Agnello L, Bivona G, Novo G, Scazzone C, Muratore R, Levantino P et al (2017) Heart-type fatty acid binding protein is a sensitive biomarker for early AMI detection in troponin negative patients: a pilot study. Scand J Clin Lab Invest 77:428–432. https://doi.org/10.1080/00365513.2017.1335880
Alcolea D, Martínez-Lage P, Sánchez-Juan P, Olazáran J, Antúnez C, Izagirre A et al (2015) Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology 85:626–633. https://doi.org/10.1212/wnl.0000000000001859
Alcolea D, Vilaplana E, Pegueroles J, Montal V, Sánchez-Juan P, González-Suárez A et al (2015) Relationship between cortical thickness and cerebrospinal fluid YKL-40 in predementia stages of Alzheimer’s disease. Neurobiol Aging 36:2018–2023. https://doi.org/10.1016/j.neurobiolaging.2015.03.001
Alcolea D, Vilaplana E, Suárez-Calvet M, Illán-Gala I, Blesa R, Clarimón J et al (2017) CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration. Neurology 89:178–188. https://doi.org/10.1212/WNL.0000000000004088
Alexopoulos P, Werle L, Roesler J, Thierjung N, Gleixner LS, Yakushev I et al (2016) Conflicting cerebrospinal fluid biomarkers and progression to dementia due to Alzheimer’s disease. Alzheimers Res Ther 8:51. https://doi.org/10.1186/s13195-016-0220-z
Association Alzheimer’s (2016) Alzheimer’s disease facts and figures. Alzheimers Dement 12:459–509
Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445. https://doi.org/10.1002/ana.21154
Anand S, Barnes JM, Young SA, Garcia DM, Tolley HD, Kauwe JSK et al (2017) Discovery and confirmation of diagnostic serum lipid biomarkers for Alzheimer’s disease using direct infusion mass spectrometry. J Alzheimers Dis 59:277–290. https://doi.org/10.3233/JAD-170035
Andreasen N, Minthon L, Vanmechelen E, Vanderstichele H, Davidsson P, Winblad B et al (1999) Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment. Neurosci Lett 273:5–8
Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S et al (1995) Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 182:155–162
Antonell A, Mansilla A, Rami L, Lladó A, Iranzo A, Olives J et al (2014) Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer’s disease. J Alzheimers Dis 42:901–908. https://doi.org/10.3233/jad-140624
Arnerić SP, Batrla-Utermann R, Beckett L, Bittner T, Blennow K, Carter L et al (2017) Cerebrospinal fluid biomarkers for Alzheimer’s disease: a view of the regulatory science qualification landscape from the Coalition Against Major Diseases CSF Biomarker Team. J Alzheimers Dis 55:19–35. https://doi.org/10.3233/JAD-160573
Ayton S, Diouf I, Bush AI, Alzheimer’s Disease Neuroimaging Initiative (2017) Evidence that iron accelerates Alzheimer’s pathology: a CSF biomarker study. J Neurol Neurosurg Psychiatry 89:456–460. https://doi.org/10.1136/jnnp-2017-316551
Ayton S, Faux NG, Bush AI (2017) Association of cerebrospinal fluid ferritin level with preclinical cognitive decline in APOE-ɛ4 carriers. JAMA Neurol 74:122–125. https://doi.org/10.1001/jamaneurol.2016.4406
Ayton S, Faux NG, Bush AI, Alzheimer’s Disease Neuroimaging Initiative (2015) Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE. Nat Commun 6:6760. https://doi.org/10.1038/ncomms7760
Ayton S, Fazlollahi A, Bourgeat P, Raniga P, Ng A, Lim YY et al (2017) Cerebral quantitative susceptibility mapping predicts amyloid-beta-related cognitive decline. Brain 140:2112–2119. https://doi.org/10.1093/brain/awx137
Babić Leko M, Borovečki F, Dejanović N, Hof PR, Ŝimić G (2016) Predictive value of cerebrospinal fluid visinin-like protein-1 levels for Alzheimer’s disease early detection and differential diagnosis in patients with mild cognitive impairment. J Alzheimers Dis 50:765–778. https://doi.org/10.3233/jad-150705
Bachurin SO, Bovina EV, Ustyugov AA (2017) Drugs in clinical trials for Alzheimer’s disease: the major trends. Med Res Rev 37:1186–1225. https://doi.org/10.1002/med.21434
Bakota L, Brandt R (2016) Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs 76:301–313. https://doi.org/10.1007/s40265-015-0529-0
Baldacci F, Lista S, Cavedo E, Bonuccelli U, Hampel H (2017) Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer’s disease and other neurodegenerative diseases. Expert Rev Proteom 14:285–299. https://doi.org/10.1080/14789450.2017.1304217
Baldacci F, Lista S, Garaci F, Bonuccelli U, Toschi N, Hampel H (2016) Biomarker-guided classification scheme of neurodegenerative diseases. J Sport Health Sci 5:383–387
Baldacci F, Lista S, O’Bryant SE, Ceravolo R, Toschi N, Hampel H et al (2018) Blood-based biomarker screening with agnostic biological definitions for an accurate diagnosis within the dimensional spectrum of neurodegenerative diseases. Methods Mol Biol 1750:139–155. https://doi.org/10.1007/978-1-4939-7704-8_9
Baldacci F, Toschi N, Lista S, Zetterberg H, Blennow K, Kilimann I et al (2017) Two-level diagnostic classification using cerebrospinal fluid YKL-40 in Alzheimer’s disease. Alzheimers Dement 13:993–1003. https://doi.org/10.1016/j.jalz.2017.01.021
Ballatore C, Brunden KR, Trojanowski JQ, Lee VM, Smith AB 3rd (2017) Non-naturally occurring small molecule microtubule-stabilizing agents: a potential tactic for CNS-directed therapies. ACS Chem Neurosci 8:5–7. https://doi.org/10.1021/acschemneuro.6b00384
Bayer TA, Wirths O (2014) Focusing the amyloid cascade hypothesis on N-truncated Abeta peptides as drug targets against Alzheimer’s disease. Acta Neuropathol 127:787–801. https://doi.org/10.1007/s00401-014-1287-x
Begcevic I, Brinc D, Brown M, Martinez-Morillo E, Goldhardt O, Grimmer T et al (2018) Brain-related proteins as potential CSF biomarkers of Alzheimer’s disease: a targeted mass spectrometry approach. J Proteom 182:12–20. https://doi.org/10.1016/j.jprot.2018.04.027
Berge G, Sando SB, Albrektsen G, Lauridsen C, Møller I, Grøntvedt GR et al (2016) Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer’s disease, mild cognitive impairment, or healthy controls: a two year follow-up study. BMC Neurol 16:180. https://doi.org/10.1186/s12883-016-0706-0
Bergman J, Dring A, Zetterberg H, Blennow K, Norgren N, Gilthorpe J et al (2016) Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol Neuroimmunol Neuroinflamm 3:e271. https://doi.org/10.1212/NXI.0000000000000271
Bettcher BM, Johnson SC, Fitch R, Casaletto KB, Heffernan KS, Asthana S et al (2018) Cerebrospinal fluid and plasma levels of inflammation differentially relate to CNS markers of Alzheimer’s disease pathology and neuronal damage. J Alzheimers Dis 62:385–397. https://doi.org/10.3233/JAD-170602
Blennow K, Bogdanovic N, Alafuzoff I, Ekman R, Davidsson P (1996) Synaptic pathology in Alzheimer’s disease: relation to severity of dementia, but not to senile plaques, neurofibrillary tangles, or the ApoE4 allele. J Neural Transm (Vienna) 103:603–618. https://doi.org/10.1007/BF01273157
Blennow K, De Meyer G, Hansson O, Minthon L, Wallin A, Zetterberg H et al (2009) Evolution of Abeta42 and Abeta40 levels and Abeta42/Abeta40 ratio in plasma during progression of Alzheimer’s disease: a multicenter assessment. J Nutr Health Aging 13:205–208
Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H (2015) Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement 11:58–69. https://doi.org/10.1016/j.jalz.2014.02.004
Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6:131–144. https://doi.org/10.1038/nrneurol.2010.4
Blennow K, Zetterberg H, Minthon L, Lannfelt L, Strid S, Annas P et al (2007) Longitudinal stability of CSF biomarkers in Alzheimer’s disease. Neurosci Lett 419:18–22. https://doi.org/10.1016/j.neulet.2007.03.064
Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ (2015) Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci 16:109–120. https://doi.org/10.1038/nrn3887
Brinkmalm A, Brinkmalm G, Honer WG, Frölich L, Hausner L, Minthon L et al (2014) SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer’s disease. Mol Neurodegener 9:53. https://doi.org/10.1186/1750-1326-9-53
Bronzuoli MR, Iacomino A, Steardo L, Scuderi C (2016) Targeting neuroinflammation in Alzheimer’s disease. J Inflamm Res 9:199–208. https://doi.org/10.2147/JIR.S86958
Brosseron F, Traschutz A, Widmann CN, Kummer MP, Tacik P, Santarelli F et al (2018) Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer’s disease. Alzheimers Res Ther 10:25. https://doi.org/10.1186/s13195-018-0353-3
Bruggink KA, Kuiperij HB, Claassen JA, Verbeek MM (2013) The diagnostic value of CSF amyloid-beta(43) in differentiation of dementia syndromes. Curr Alzheimer Res 10:1034–1040
Brunden KR, Zhang B, Carroll J, Yao Y, Potuzak JS, Hogan AM et al (2010) Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci 30:13861–13866. https://doi.org/10.1523/jneurosci.3059-10.2010
Buchhave P, Blennow K, Zetterberg H, Stomrud E, Londos E, Andreasen N, Minthon L et al (2009) Longitudinal study of CSF biomarkers in patients with Alzheimer’s disease. PLoS One 4:e6294. https://doi.org/10.1371/journal.pone.0006294
Budd Haeberlein S, O’Gorman J, Chiao P, Bussiere T, von Rosenstiel P, Tian Y et al (2017) Clinical development of aducanumab, an anti-Abeta human monoclonal antibody being investigated for the treatment of early Alzheimer’s disease. J Prev Alzheimers Dis 4:255–263. https://doi.org/10.14283/jpad.2017.39
Byrne LM, Rodrigues FB, Blennow K, Durr A, Leavitt BR, Roos RAC et al (2017) Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysis. Lancet Neurol 16:601–609. https://doi.org/10.1016/s1474-4422(17)30124-2
Calsolaro V, Edison P (2016) Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement 12:719–732. https://doi.org/10.1016/j.jalz.2016.02.010
Carroll CM, Li YM (2016) Physiological and pathological roles of the γ-secretase complex. Brain Res Bull 126:199–206. https://doi.org/10.1016/j.brainresbull.2016.04.019
Castrillo JI, Lista S, Hampel H, Ritchie CW (2018) Systems biology methods for Alzheimer’s disease research toward molecular signatures, subtypes, and stages and precision medicine: application in cohort studies and trials. Methods Mol Biol 1750:31–66. https://doi.org/10.1007/978-1-4939-7704-8_3
Catafau AM, Bullich S (2017) Non-amyloid PET imaging biomarkers for neurodegeneration: focus on tau, alpha-synuclein and neuroinflammation. Curr Alzheimer Res 14:169–177
Chakraborty A, de Wit NM, van der Flier WM, de Vries HE (2017) The blood brain barrier in Alzheimer’s disease. Vascul Pharmacol 89:12–18. https://doi.org/10.1016/j.vph.2016.11.008
Chang KA, Shin KY, Nam E, Lee YB, Moon C, Suh YH et al (2016) Plasma soluble neuregulin-1 as a diagnostic biomarker for Alzheimer’s disease. Neurochem Int 97:1–7. https://doi.org/10.1016/j.neuint.2016.04.012
Chang XL, Tan MS, Tan L, Yu JT (2016) The role of TDP-43 in Alzheimer’s disease. Mol Neurobiol 53:3349–3359. https://doi.org/10.1007/s12035-015-9264-5
Chen-Plotkin AS, Lee VM, Trojanowski JQ (2010) TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol 6:211–220. https://doi.org/10.1038/nrneurol.2010.18
Chen Z, Trapp BD (2016) Microglia and neuroprotection. J Neurochem 136(Suppl 1):10–17. https://doi.org/10.1111/jnc.13062
Chiasserini D, Biscetti L, Eusebi P, Salvadori N, Frattini G, Simoni S et al (2017) Differential role of CSF fatty acid binding protein 3, α-synuclein, and Alzheimer’s disease core biomarkers in Lewy body disorders and Alzheimer’s dementia. Alzheimers Res Ther 9:52. https://doi.org/10.1186/s13195-017-0276-4
Choi J, Lee HW, Suk K (2011) Plasma level of chitinase 3-like 1 protein increases in patients with early Alzheimer’s disease. J Neurol 258:2181–2185. https://doi.org/10.1007/s00415-011-6087-9
Cornett CR, Markesbery WR, Ehmann WD (1998) Imbalances of trace elements related to oxidative damage in Alzheimer’s disease brain. Neurotoxicology 19:339–345
Corso G, Cristofano A, Sapere N, la Marca G, Angiolillo A, Vitale M et al (2017) Serum amino acid profiles in normal subjects and in patients with or at risk of Alzheimer dementia. Dement Geriatr Cogn Dis Extra 7:143–159. https://doi.org/10.1159/000466688
Craig-Schapiro R, Perrin RJ, Roe CM, Xiong C, Carter D, Cairns NJ et al (2010) YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry 68:903–912. https://doi.org/10.1016/j.biopsych.2010.08.025
Cristóvão JS, Santos R, Gomes CM (2016) Metals and neuronal metal binding proteins implicated in Alzheimer’s disease. Oxid Med Cell Longev 2016:9812178. https://doi.org/10.1155/2016/9812178
Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM et al (2013) GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer’s disease. Neuron 78:256–268. https://doi.org/10.1016/j.neuron.2013.02.026
Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K (2017) Alzheimer’s disease drug development pipeline: 2017. Alzheimers Dement (N Y) 3:367–384. https://doi.org/10.1016/j.trci.2017.05.002
Dage JL, Wennberg AM, Airey DC, Hagen CE, Knopman DS, Machulda MM et al (2016) Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort. Alzheimers Dement 12:1226–1234. https://doi.org/10.1016/j.jalz.2016.06.001
Davidsson P, Blennow K (1998) Neurochemical dissection of synaptic pathology in Alzheimer’s disease. Int Psychogeriatr 10:11–23
De Vos A, Jacobs D, Struyfs H, Fransen E, Andersson K, Portelius E et al (2015) C-terminal neurogranin is increased in cerebrospinal fluid but unchanged in plasma in Alzheimer’s disease. Alzheimers Dement 11:1461–1469. https://doi.org/10.1016/j.jalz.2015.05.012
De Vos A, Struyfs H, Jacobs D, Fransen E, Klewansky T, De Roeck E et al (2016) The cerebrospinal fluid neurogranin/BACE1 ratio is a potential correlate of cognitive decline in Alzheimer’s disease. J Alzheimers Dis 53:1523–1538. https://doi.org/10.3233/jad-160227
Degerman Gunnarsson M, Ingelsson M, Blennow K, Basun H, Lannfelt L, Kilander L (2016) High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease. Alzheimers Res Ther 8:22. https://doi.org/10.1186/s13195-016-0191-0
Delgado-Alvarado M, Gago B, Gorostidi A, Jiménez-Urbieta H, Dacosta-Aguayo R, Navalpotro-Gómez I et al (2017) Tau/alpha-synuclein ratio and inflammatory proteins in Parkinson’s disease: an exploratory study. Mov Disord 32:1066–1073. https://doi.org/10.1002/mds.27001
Desikan RS, Thompson WK, Holland D, Hess CP, Brewer JB, Zetterberg H et al (2013) Heart fatty acid binding protein and Aβ-associated Alzheimer’s neurodegeneration. Mol Neurodegener 8:39. https://doi.org/10.1186/1750-1326-8-39
Deters KD, Risacher SL, Kim S, Nho K, West JD, Blennow K et al (2017) Plasma tau association with brain atrophy in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 58:1245–1254. https://doi.org/10.3233/JAD-161114
Di Marco LY, Venneri A, Farkas E, Evans PC, Marzo A, Frangi AF (2015) Vascular dysfunction in the pathogenesis of Alzheimer’s disease—a review of endothelium-mediated mechanisms and ensuing vicious circles. Neurobiol Dis 82:593–606. https://doi.org/10.1016/j.nbd.2015.08.014
Díez-Guerra FJ (2010) Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity. IUBMB Life 62:597–606. https://doi.org/10.1002/iub.357
Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A et al (2017) Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol 81:857–870. https://doi.org/10.1002/ana.24954
Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S et al (2014) Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 370:311–321. https://doi.org/10.1056/NEJMoa1312889
Dorey A, Perret-Liaudet A, Tholance Y, Fourier A, Quadrio I (2015) Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. Front Neurol 6:247. https://doi.org/10.3389/fneur.2015.00247
Downes EC, Robson J, Grailly E, Abdel-All Z, Xuereb J, Brayne C et al (2008) Loss of synaptophysin and synaptosomal-associated protein 25-kDa (SNAP-25) in elderly down syndrome individuals. Neuropathol Appl Neurobiol 34:12–22. https://doi.org/10.1111/j.1365-2990.2007.00899.x
Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K et al (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13:614–629. https://doi.org/10.1016/s1474-4422(14)70090-0
Engelborghs S, Niemantsverdriet E, Struyfs H, Blennow K, Brouns R, Comabella M et al (2017) Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst) 8:111–126. https://doi.org/10.1016/j.dadm.2017.04.007
European Medicines Agency, Committee for Medicinal Products for Human Use (2011) Qualification opinion of Alzheimer’s disease novel methodologies/biomarkers for the use of CSF amyloid beta 1-42 and t-tau signature and/or PET-amyloid imaging (positive/negative) as biomarkers for enrichment, for use in regulatory clinical trials in mild and moderate Alzheimer’s disease. http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2011/12/WC500118365.pdf
European Medicines Agency, Committee for Medicinal Products for Human Use (2018) Guideline on the clinical investigation of medicines for the treatment of Alzheimer’s disease. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2018/02/WC500244609.pdf
Ewers M, Cheng X, Zhong Z, Nural HF, Walsh C, Meindl T et al (2011) Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer’s disease. J Alzheimers Dis 25:373–381. https://doi.org/10.3233/jad-2011-091153
Ewers M, Mattsson N, Minthon L, Molinuevo JL, Antonell A, Popp J et al (2015) CSF biomarkers for the differential diagnosis of Alzheimer’s disease: a large-scale international multicenter study. Alzheimers Dement 11:1306–1315. https://doi.org/10.1016/j.jalz.2014.12.006
Ewers M, Zhong Z, Bürger K, Wallin A, Blennow K, Teipel SJ et al (2008) Increased CSF-BACE 1 activity is associated with ApoE-ε4 genotype in subjects with mild cognitive impairment and Alzheimer’s disease. Brain 131:1252–1258. https://doi.org/10.1093/brain/awn034
Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR et al (2006) Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ42 in humans. Ann Neurol 59:512–519. https://doi.org/10.1002/ana.20730
Fagan AM, Mintun MA, Shah AR, Aldea P, Roe CM, Mach RH et al (2009) Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer’s disease. EMBO Mol Med 1:371–380. https://doi.org/10.1002/emmm.200900048
Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM (2007) Cerebrospinal fluid tau/β-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64:343–349. https://doi.org/10.1001/archneur.64.3.noc60123
Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ et al (2011) Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol 68:1137–1144. https://doi.org/10.1001/archneurol.2011.105
Fairfoul G, McGuire LI, Pal S, Ironside JW, Neumann J, Christie S et al (2016) Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Transl Neurol 3:812–818. https://doi.org/10.1002/acn3.338
Fandos N, Pérez-Grijalba V, Pesini P, Olmos S, Bossa M, Villemagne VL et al (2017) Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals. Alzheimers Dement (Amst) 8:179–187. https://doi.org/10.1016/j.dadm.2017.07.004
Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP et al (2012) Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement 8:261–271. https://doi.org/10.1016/j.jalz.2011.09.224
Fath T, Eidenmuller J, Brandt R (2002) Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer’s disease. J Neurosci 22:9733–9741
Feneberg E, Steinacker P, Lehnert S, Schneider A, Walther P, Thal DR et al (2014) Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases. Amyotroph Lateral Scler Frontotemporal Degener 15:351–356. https://doi.org/10.3109/21678421.2014.905606
Ferreira D, Rivero-Santana A, Perestelo-Pérez L, Westman E, Wahlund LO, Sarría A et al (2014) Improving CSF biomarkers’ performance for predicting progression from mild cognitive impairment to Alzheimer’s disease by considering different confounding factors: a meta-analysis. Front Aging Neurosci 6:287. https://doi.org/10.3389/fnagi.2014.00287
Ferretti M, Lulita M, Cavedo E, Chiesa P, Schumacher Dimech A, Chadha Santuccione A et al (2018) Sex-specific phenotypes of Alzheimer’s disease: the gateway to precision neurology. Nat Rev Neurol 14:457–469. https://doi.org/10.1038/s41582-018-0032-9
Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK et al (2016) Imaging synaptic density in the living human brain. Sci Transl Med 8:348ra396. https://doi.org/10.1126/scitranslmed.aaf6667
Fleck D, van Bebber F, Colombo A, Galante C, Schwenk BM, Rabe L et al (2013) Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling. J Neurosci 33:7856–7869. https://doi.org/10.1523/JNEUROSCI.3372-12.2013
Food and Drug Administration (2011) Guidance for industry—E16 biomarkers related to drug or biotechnology product development: context, structure, and format of qualification submissions. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm267449.pdf
Food and Drug Administration (2018) Early Alzheimer’s disease: developing drugs for treatment; draft guidance for industry. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf
Foulds P, McAuley E, Gibbons L, Davidson Y, Pickering-Brown SM, Neary D et al (2008) TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer’s disease and frontotemporal lobar degeneration. Acta Neuropathol 116:141–146. https://doi.org/10.1007/s00401-008-0389-8
Fourier A, Portelius E, Zetterberg H, Blennow K, Quadrio I, Perret-Liaudet A (2015) Pre-analytical and analytical factors influencing Alzheimer’s disease cerebrospinal fluid biomarker variability. Clin Chim Acta 449:9–15. https://doi.org/10.1016/j.cca.2015.05.024
Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, Mehta PD et al (2003) Biological markers for therapeutic trials in Alzheimer’s disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer’s disease. Neurobiol Aging 24:521–536
Frisoni GB, Boccardi M, Barkhof F, Blennow K, Cappa S, Chiotis K et al (2017) Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol 16:661–676. https://doi.org/10.1016/S1474-4422(17)30159-X
Galimberti D, Schoonenboom N, Scheltens P, Fenoglio C, Bouwman F, Venturelli E et al (2006) Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol 63:538–543. https://doi.org/10.1001/archneur.63.4.538
Galimberti D, Venturelli E, Fenoglio C, Lovati C, Guidi I, Scalabrini D et al (2007) IP-10 serum levels are not increased in mild cognitive impairment and Alzheimer’s disease. Eur J Neurol 14:e3–e4. https://doi.org/10.1111/j.1468-1331.2006.01637.x
Gendron TF, C9ORF72 Neurofilament Study Group, Daughrity LM, Heckman MG, Diehl NN, Wuu J et al (2017) Phosphorylated neurofilament heavy chain: a biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Ann Neurol 82:139–146. https://doi.org/10.1002/ana.24980
Gervaise-Henry C, Watfa G, Albuisson E, Kolodziej A, Dousset B, Olivier JL et al (2017) Cerebrospinal fluid Aβeta42/Aβeta40 as a means to limiting tube- and storage-dependent pre-analytical variability in clinical setting. J Alzheimers Dis 57:437–445. https://doi.org/10.3233/jad-160865
Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT et al (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300:636–640. https://doi.org/10.1126/science.1082324
Gispert JD, Monte GC, Suárez-Calvet M, Falcon C, Tucholka A, Rojas S et al (2017) The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer’s disease but not those of sTREM2. Alzheimers Dement (Amst) 6:50–59. https://doi.org/10.1016/j.dadm.2016.12.002
Gispert JD, Suárez-Calvet M, Monté GC, Tucholka A, Falcon C, Rojas S et al (2016) Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer’s disease. Alzheimers Dement 12:1259–1272. https://doi.org/10.1016/j.jalz.2016.06.005
Glenner GG, Wong CW (1984) Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1135
Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890
Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL et al (2016) Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J 30:4141–4148. https://doi.org/10.1096/fj.201600816R
Goossens J, Vanmechelen E, Trojanowski JQ, Lee VM, Van Broeckhoven C, van der Zee J et al (2015) TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a systematic review of existing antibodies. Acta Neuropathol Commun 3:15. https://doi.org/10.1186/s40478-015-0195-1
Goozee K, Chatterjee P, James I, Shen K, Sohrabi HR, Asih PR et al (2018) Elevated plasma ferritin in elderly individuals with high neocortical amyloid-beta load. Mol Psychiatry 23:1807–1812. https://doi.org/10.1038/mp.2017.146
Gravina SA, Ho L, Eckman CB, Long KE, Otvos L Jr, Younkin LH et al (1995) Amyloid beta protein (A beta) in Alzheimer’s disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43). J Biol Chem 270:7013–7016
Grimmer T, Riemenschneider M, Förstl H, Henriksen G, Klunk WE, Mathis CA et al (2009) Beta amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry 65:927–934. https://doi.org/10.1016/j.biopsych.2009.01.027
Groblewska M, Muszynski P, Wojtulewska-Supron A, Kulczynska-Przybik A, Mroczko B (2015) The role of visinin-like protein-1 in the pathophysiology of Alzheimer’s disease. J Alzheimers Dis 47:17–32. https://doi.org/10.3233/jad-150060
Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E et al (2013) TREM2 variants in Alzheimer’s disease. N Engl J Med 368:117–127. https://doi.org/10.1056/NEJMoa1211851
Gunn AP, Masters CL, Cherny RA (2010) Pyroglutamate-Aβ: role in the natural history of Alzheimer’s disease. Int J Biochem Cell Biol 42:1915–1918. https://doi.org/10.1016/j.biocel.2010.08.015
Guo JL, Lee VM (2014) Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med 20:130–138. https://doi.org/10.1038/nm.3457
Guo LH, Alexopoulos P, Perneczky R (2013) Heart-type fatty acid binding protein and vascular endothelial growth factor: cerebrospinal fluid biomarker candidates for Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 263:553–560. https://doi.org/10.1007/s00406-013-0405-4
Guo R, Fan G, Zhang J, Wu C, Du Y, Ye H et al (2017) A 9-microRNA signature in serum serves as a noninvasive biomarker in early diagnosis of Alzheimer’s disease. J Alzheimers Dis 60:1365–1377. https://doi.org/10.3233/JAD-170343
Hamilton RL (2000) Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol 10:378–384
Hampel H, Bürger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K (2008) Core candidate neurochemical and imaging biomarkers of Alzheimer’s disease. Alzheimers Dement 4:38–48. https://doi.org/10.1016/j.jalz.2007.08.006
Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J et al (2010) Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov 9:560–574. https://doi.org/10.1038/nrd3115
Hampel H, Lista S, Khachaturian ZS (2012) Development of biomarkers to chart all Alzheimer’s disease stages: the royal road to cutting the therapeutic Gordian Knot. Alzheimers Dement 8:312–336. https://doi.org/10.1016/j.jalz.2012.05.2116
Hampel H, Lista S, Teipel SJ, Garaci F, Nisticó R, Blennow K et al (2014) Perspective on future role of biological markers in clinical therapy trials of Alzheimer’s disease: a long-range point of view beyond 2020. Biochem Pharmacol 88:426–449. https://doi.org/10.1016/j.bcp.2013.11.009
Hampel H, O’Bryant SE, Castrillo JI, Ritchie C, Rojkova K, Broich K et al (2016) PRECISION MEDICINE—the Golden Gate for detection, treatment and prevention of Alzheimer’s disease. J Prev Alzheimers Dis 3:243–259. https://doi.org/10.14283/jpad.2016.112
Hampel H, O’Bryant SE, Durrleman S, Younesi E, Rojkova K, Escott-Price V et al (2017) A precision medicine initiative for Alzheimer’s disease: the road ahead to biomarker-guided integrative disease modeling. Climacteric 20:107–118. https://doi.org/10.1080/13697137.2017.1287866
Hampel H, O’Bryant SE, Molinuevo JL, Zetterberg H, Masters CL, Lista S et al (2018) Blood-based biomarkers for Alzheimer’s disease: mapping the road to the clinic. Nat Rev Neurol 14:639–652. https://doi.org/10.1038/s41582-018-0079-7
Hampel H, Toschi N, Babiloni C, Baldacci F, Black KL, Bokde ALW et al (2018) Revolution of Alzheimer precision neurology. Passageway of systems biology and neurophysiology. J Alzheimers Dis 64(Suppl 1):S47–S105. https://doi.org/10.3233/JAD-179932
Hampel H, Vergallo A, Aguilar LF, Benda N, Broich K, Cuello AC et al (2018) Precision pharmacology for Alzheimer’s disease. Pharmacol Res 130:331–365. https://doi.org/10.1016/j.phrs.2018.02.014
Han J, Pluhackova K, Böckmann RA (2017) The multifaceted role of SNARE proteins in membrane fusion. Front Physiol 8:5. https://doi.org/10.3389/fphys.2017.00005
Hansson O, Hall S, Ohrfelt A, Zetterberg H, Blennow K, Minthon L et al (2014) Levels of cerebrospinal fluid α-synuclein oligomers are increased in Parkinson’s disease with dementia and dementia with Lewy bodies compared to Alzheimer’s disease. Alzheimers Res Ther 6:25. https://doi.org/10.1186/alzrt255
Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L (2006) Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5:228–234. https://doi.org/10.1016/S1474-4422(06)70355-6
Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185
Hare D, Ayton S, Bush A, Lei P (2013) A delicate balance: iron metabolism and diseases of the brain. Front Aging Neurosci 5:34. https://doi.org/10.3389/fnagi.2013.00034
He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L et al (2018) Amyloid-β plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24:29–38. https://doi.org/10.1038/nm.4443
Heinonen O, Soininen H, Sorvari H, Kosunen O, Paljärvi L, Koivisto E et al (1995) Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in Alzheimer’s disease. Neuroscience 64:375–384
Hellwig K, Kvartsberg H, Portelius E, Andreasson U, Oberstein TJ, Lewczuk P et al (2015) Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther 7:74. https://doi.org/10.1186/s13195-015-0161-y
Henjum K, Almdahl IS, Årskog V, Minthon L, Hansson O, Fladby T et al (2016) Cerebrospinal fluid soluble TREM2 in aging and Alzheimer’s disease. Alzheimers Res Ther 8:17. https://doi.org/10.1186/s13195-016-0182-1
Henriksen K, O’Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A et al (2014) The future of blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement 10:115–131. https://doi.org/10.1016/j.jalz.2013.01.013
Heslegrave A, Heywood W, Paterson R, Magdalinou N, Svensson J, Johansson P et al (2016) Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease. Mol Neurodegener 11:3. https://doi.org/10.1186/s13024-016-0071-x
Hesse R, Wahler A, Gummert P, Kirschmer S, Otto M, Tumani H et al (2016) Decreased IL-8 levels in CSF and serum of AD patients and negative correlation of MMSE and IL-1β. BMC Neurol 16:185. https://doi.org/10.1186/s12883-016-0707-z
Hölttä M, Hansson O, Andreasson U, Hertze J, Minthon L, Nägga K et al (2013) Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer’s disease. PLoS One 8:e66381. https://doi.org/10.1371/journal.pone.0066381
Horrocks MH, Lee SF, Gandhi S, Magdalinou NK, Chen SW, Devine MJ et al (2016) Single-molecule imaging of individual amyloid protein aggregates in human biofluids. ACS Chem Neurosci 7:399–406. https://doi.org/10.1021/acschemneuro.5b00324
Hu N, Tan MS, Yu JT, Sun L, Tan L, Wang YL et al (2014) Increased expression of TREM2 in peripheral blood of Alzheimer’s disease patients. J Alzheimers Dis 38:497–501. https://doi.org/10.3233/jad-130854
Hu WT, Chen-Plotkin A, Arnold SE, Grossman M, Clark CM, Shaw LM et al (2010) Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment. Acta Neuropathol 119:669–678. https://doi.org/10.1007/s00401-010-0667-0
Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC et al (1999) The A beta peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38:7609–7616. https://doi.org/10.1021/bi990438f
Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP et al (1999) Improved discrimination of AD patients using β-amyloid(1-42) and tau levels in CSF. Neurology 52:1555–1562
Huynh RA, Mohan C (2017) Alzheimer’s disease: biomarkers in the genome, blood, and cerebrospinal fluid. Front Neurol 8:102. https://doi.org/10.3389/fneur.2017.00102
Inekci D, Henriksen K, Linemann T, Karsdal MA, Habib A, Bisgaard C et al (2015) Serum fragments of tau for the differential diagnosis of Alzheimer’s disease. Curr Alzheimer Res 12:829–836
Ingelsson M (2016) Alpha-synuclein oligomers-neurotoxic molecules in Parkinson’s disease and other Lewy body disorders. Front Neurosci 10:408. https://doi.org/10.3389/fnins.2016.00408
Irwin DJ (2016) Tauopathies as clinicopathological entities. Parkinsonism Relat Disord 22(Suppl 1):S29–S33. https://doi.org/10.1016/j.parkreldis.2015.09.020
Isaac M, Vamvakas S, Abadie E, Jonsson B, Gispen C, Pani L (2011) Qualification opinion of novel methodologies in the predementia stage of Alzheimer’s disease: cerebro-spinal-fluid related biomarkers for drugs affecting amyloid burden—regulatory considerations by European Medicines Agency focusing in improving benefit/risk in regulatory trials. Eur Neuropsychopharmacol 21:781–788. https://doi.org/10.1016/j.euroneuro.2011.08.003
Iturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-Pérez JM, Evans AC, Alzheimer’s Disease Neuroimaging Initiative (2016) Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nat Commun 7:11934. https://doi.org/10.1038/ncomms11934
Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: evidence that an initially deposited species is Aβ42(43). Neuron 13:45–53
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS et al (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12:207–216. https://doi.org/10.1016/S1474-4422(12)70291-0
Jackson K, Barisone GA, Diaz E, Jin LW, DeCarli C, Despa F (2013) Amylin deposition in the brain: a second amyloid in Alzheimer disease? Ann Neurol 74:517–526. https://doi.org/10.1002/ana.23956
Jagust WJ, Landau SM, Shaw LM, Trojanowski JQ, Koeppe RA, Reiman EM et al (2009) Relationships between biomarkers in aging and dementia. Neurology 73:1193–1199. https://doi.org/10.1212/WNL.0b013e3181bc010c
James BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA (2016) TDP-43 stage, mixed pathologies, and clinical Alzheimer’s-type dementia. Brain 139:2983–2993. https://doi.org/10.1093/brain/aww224
Janelidze S, Stomrud E, Palmqvist S, Zetterberg H, van Westen D, Jeromin A et al (2016) Plasma β-amyloid in Alzheimer’s disease and vascular disease. Sci Rep 6:26801. https://doi.org/10.1038/srep26801
Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O et al (2016) CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol 3:154–165. https://doi.org/10.1002/acn3.274
Jay TR, von Saucken VE, Landreth GE (2017) TREM2 in neurodegenerative diseases. Mol Neurodegener 12:56. https://doi.org/10.1186/s13024-017-0197-5
Josephs KA, Whitwell JL, Knopman DS, Hu WT, Stroh DA, Baker M et al (2008) Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 70:1850–1857. https://doi.org/10.1212/01.wnl.0000304041.09418.b1
Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501:45–51. https://doi.org/10.1038/nature12481
Junttila A, Kuvaja M, Hartikainen P, Siloaho M, Helisalmi S, Moilanen V et al (2016) Cerebrospinal fluid TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis patients with and without the C9ORF72 hexanucleotide expansion. Dement Geriatr Cogn Dis Extra 6:142–149. https://doi.org/10.1159/000444788
Kakuda N, Miyasaka T, Iwasaki N, Nirasawa T, Wada-Kakuda S, Takahashi-Fujigasaki J et al (2017) Distinct deposition of amyloid-beta species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry. Acta Neuropathol Commun 5:73. https://doi.org/10.1186/s40478-017-0477-x
Kamat PK, Kalani A, Rai S, Swarnkar S, Tota S, Nath C et al (2016) Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease: understanding the therapeutics strategies. Mol Neurobiol 53:648–661. https://doi.org/10.1007/s12035-014-9053-6
Kang JH, Irwin DJ, Chen-Plotkin AS, Siderowf A, Caspell C, Coffey CS et al (2013) Association of cerebrospinal fluid β-amyloid 1-42, t-tau, p-tau181, and α-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol 70:1277–1287. https://doi.org/10.1001/jamaneurol.2013.3861
Kang JH, Mollenhauer B, Coffey CS, Toledo JB, Weintraub D, Galasko DR et al (2016) CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study. Acta Neuropathol 131:935–949. https://doi.org/10.1007/s00401-016-1552-2
Kapaki E, Paraskevas GP, Emmanouilidou E, Vekrellis K (2013) The diagnostic value of CSF α-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer’s disease. PLoS One 8:e81654. https://doi.org/10.1371/journal.pone.0081654
Kasai T, Tokuda T, Ishii R, Ishigami N, Tsuboi Y, Nakagawa M et al (2014) Increased α-synuclein levels in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. J Neurol 261:1203–1209. https://doi.org/10.1007/s00415-014-7334-7
Kasuga K, Tokutake T, Ishikawa A, Uchiyama T, Tokuda T, Onodera O et al (2010) Differential levels of α-synuclein, β-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 81:608–610. https://doi.org/10.1136/jnnp.2009.197483
Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF et al (2016) The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients. Sci Transl Med 8:363ra150. https://doi.org/10.1126/scitranslmed.aad9704
Kerchner G, Ayalon G, Blendstrup M, Brunstein F, Chandra P, Datwani A et al (2017) Targeting tau with RO7105705: Phase I results and design of a Phase II study in prodromal-to-mild AD. Abstract presented at the 10th Clinical Trials on Alzheimer’s Disease (CTAD). Boston (1–4 November 2017)
Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P et al (2015) Neurogranin as a cerebrospinal fluid biomarker for synaptic loss in symptomatic Alzheimer disease. JAMA Neurol 72:1275–1280. https://doi.org/10.1001/jamaneurol.2015.1867
Kester MI, Teunissen CE, Sutphen C, Herries EM, Ladenson JH, Xiong C et al (2015) Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer’s disease in a memory clinic cohort. Alzheimers Res Ther 7:59. https://doi.org/10.1186/s13195-015-0142-1
Khan SS, Bloom GS (2016) Tau: the center of a signaling nexus in Alzheimer’s disease. Front Neurosci 10:31. https://doi.org/10.3389/fnins.2016.00031
Kim D, Kim YS, Shin DW, Park CS, Kang JH (2016) Harnessing cerebrospinal fluid biomarkers in clinical trials for treating Alzheimer’s and Parkinson’s diseases: potential and challenges. J Clin Neurol 12:381–392. https://doi.org/10.3988/jcn.2016.12.4.381
Kim HJ, Park KW, Kim TE, Im JY, Shin HS, Kim S et al (2015) Elevation of the plasma Aβ40/Aβ42 ratio as a diagnostic marker of sporadic early-onset Alzheimer’s disease. J Alzheimers Dis 48:1043–1050. https://doi.org/10.3233/JAD-143018
Kim J, Onstead L, Randle S, Price R, Smithson L, Zwizinski C et al (2007) Aβ40 inhibits amyloid deposition in vivo. J Neurosci 27:627–633. https://doi.org/10.1523/jneurosci.4849-06.2007
Kim WS, Kågedal K, Halliday GM (2014) Alpha-synuclein biology in Lewy body diseases. Alzheimers Res Ther 6:73. https://doi.org/10.1186/s13195-014-0073-2
Komori M, Kosa P, Stein J, Zhao V, Blake A, Cherup J et al (2017) Pharmacodynamic effects of daclizumab in the intrathecal compartment. Ann Clin Transl Neurol 4:478–490. https://doi.org/10.1002/acn3.427
Korff A, Liu C, Ginghina C, Shi M, Zhang J, Initiative Alzheimer’s Disease Neuroimaging (2013) α-Synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis 36:679–688. https://doi.org/10.3233/jad-130458
Kuhle J, Nourbakhsh B, Grant D, Morant S, Barro C, Yaldizli O et al (2017) Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology 88:826–831. https://doi.org/10.1212/wnl.0000000000003653
Kuhlmann J, Andreasson U, Pannee J, Bjerke M, Portelius E, Leinenbach A et al (2017) CSF Abeta1-42—an excellent but complicated Alzheimer’s biomarker—a route to standardisation. Clin Chim Acta 467:27–33. https://doi.org/10.1016/j.cca.2016.05.014
Kuhn PH, Koroniak K, Hogl S, Colombo A, Zeitschel U, Willem M et al (2012) Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons. EMBO J 31:3157–3168. https://doi.org/10.1038/emboj.2012.173
Kuiperij HB, Versleijen AA, Beenes M, Verwey NA, Benussi L, Paterlini A et al (2017) Tau rather than TDP-43 proteins are potential cerebrospinal fluid biomarkers for frontotemporal lobar degeneration subtypes: a pilot study. J Alzheimers Dis 55:585–595. https://doi.org/10.3233/jad-160386
Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M et al (2010) Neurotoxicity of Alzheimer’s disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio. EMBO J 29:3408–3420. https://doi.org/10.1038/emboj.2010.211
Kvartsberg H, Duits FH, Ingelsson M, Andreasen N, Öhrfelt A, Andersson K et al (2015) Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer’s disease. Alzheimers Dement 11:1180–1190. https://doi.org/10.1016/j.jalz.2014.10.009
Kvartsberg H, Portelius E, Andreasson U, Brinkmalm G, Hellwig K, Lelental N et al (2015) Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer’s disease patients and healthy controls. Alzheimers Res Ther 7:40. https://doi.org/10.1186/s13195-015-0124-3
Lai KSP, Liu CS, Rau A, Lanctot KL, Kohler CA, Pakosh M et al (2017) Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 88:876–882. https://doi.org/10.1136/jnnp-2017-316201
Laterza OF, Modur VR, Crimmins DL, Olander JV, Landt Y, Lee JM et al (2006) Identification of novel brain biomarkers. Clin Chem 52:1713–1721. https://doi.org/10.1373/clinchem.2006.070912
Lauridsen C, Sando SB, Moller I, Berge G, Pomary PK, Grontvedt GR et al (2017) Cerebrospinal fluid Abeta43 Is reduced in early-onset compared to late-onset Alzheimer’s Disease, but has similar diagnostic accuracy to Abeta42. Front Aging Neurosci 9:210. https://doi.org/10.3389/fnagi.2017.00210
Lee JM, Blennow K, Andreasen N, Laterza O, Modur V, Olander J et al (2008) The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clin Chem 54:1617–1623. https://doi.org/10.1373/clinchem.2008.104497
Lee PH, Lee G, Park HJ, Bang OY, Joo IS, Huh K (2006) The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy. J Neural Transm (Vienna) 113:1435–1439. https://doi.org/10.1007/s00702-005-0427-9
Lee VM, Balin BJ, Otvos L Jr, Trojanowski JQ (1991) A68: a major subunit of paired helical filaments and derivatized forms of normal tau. Science 251:675–678
Lee VM, Trojanowski JQ (2001) Transgenic mouse models of tauopathies: prospects for animal models of Pick’s disease. Neurology 56:S26–S30
Leitão MJ, Baldeiras I, Herukka SK, Pikkarainen M, Leinonen V, Simonsen AH et al (2015) Chasing the effects of pre-analytical confounders—a multicenter study on CSF-AD biomarkers. Front Neurol 6:153. https://doi.org/10.3389/fneur.2015.00153
Lemstra AW, de Beer MH, Teunissen CE, Schreuder C, Scheltens P, van der Flier WM et al (2017) Concomitant AD pathology affects clinical manifestation and survival in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 88:113–118. https://doi.org/10.1136/jnnp-2016-313775
Leschik J, Welzel A, Weissmann C, Eckert A, Brandt R (2007) Inverse and distinct modulation of tau-dependent neurodegeneration by presenilin 1 and amyloid-β in cultured cortical neurons: evidence that tau phosphorylation is the limiting factor in amyloid-β-induced cell death. J Neurochem 101:1303–1315. https://doi.org/10.1111/j.1471-4159.2006.04435.x
Leung YY, Toledo JB, Nefedov A, Polikar R, Raghavan N, Xie SX et al (2015) Identifying amyloid pathology-related cerebrospinal fluid biomarkers for Alzheimer’s disease in a multicohort study. Alzheimers Dement (Amst) 1:339–348. https://doi.org/10.1016/j.dadm.2015.06.008
Leuzy A, Chiotis K, Hasselbalch SG, Rinne JO, de Mendonça A, Otto M et al (2016) Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study. Brain 139:2540–2553. https://doi.org/10.1093/brain/aww160
Leverenz JB, Fishel MA, Peskind ER, Montine TJ, Nochlin D, Steinbart E et al (2006) Lewy body pathology in familial Alzheimer disease: evidence for disease- and mutation-specific pathologic phenotype. Arch Neurol 63:370–376. https://doi.org/10.1001/archneur.63.3.370
Lewczuk P, Lelental N, Lachmann I, Holzer M, Flach K, Brandner S et al (2017) Non-phosphorylated tau as a potential biomarker of Alzheimer’s disease: analytical and diagnostic characterization. J Alzheimers Dis 55:159–170. https://doi.org/10.3233/JAD-160448
Lewczuk P, Matzen A, Blennow K, Parnetti L, Molinuevo JL, Eusebi P et al (2017) Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease. J Alzheimers Dis 55:813–822. https://doi.org/10.3233/jad-160722
Lewczuk P, Riederer P, O’Bryant SE, Verbeek MM, Dubois B, Visser PJ et al (2017) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry. https://doi.org/10.1080/15622975.2017.1375556
Lewis KA, Su Y, Jou O, Ritchie C, Foong C, Hynan LS et al (2010) Abnormal neurites containing C-terminally truncated alpha-synuclein are present in Alzheimer’s disease without conventional Lewy body pathology. Am J Pathol 177:3037–3050. https://doi.org/10.2353/ajpath.2010.100552
Leyhe T, Andreasen N, Simeoni M, Reich A, von Arnim CA, Tong X et al (2014) Modulation of beta-amyloid by a single dose of GSK933776 in patients with mild Alzheimer’s disease: a phase I study. Alzheimers Res Ther 6:19. https://doi.org/10.1186/alzrt249
Li G, Sokal I, Quinn JF, Leverenz JB, Brodey M, Schellenberg GD et al (2007) CSF tau/Aβ42 ratio for increased risk of mild cognitive impairment: a follow-up study. Neurology 69:631–639. https://doi.org/10.1212/01.wnl.0000267428.62582.aa
Li X, Lei P, Tuo Q, Ayton S, Li QX, Moon S et al (2015) Enduring elevations of hippocampal amyloid precursor protein and iron are features of β-amyloid toxicity and are mediated by tau. Neurotherapeutics 12:862–873. https://doi.org/10.1007/s13311-015-0378-2
Libreros S, Iragavarapu-Charyulu V (2015) YKL-40/CHI3L1 drives inflammation on the road of tumor progression. J Leukoc Biol 98:931–936. https://doi.org/10.1189/jlb.3VMR0415-142R
Lin CH, Yang SY, Horng HE, Yang CC, Chieh JJ, Chen HH et al (2017) Plasma α-synuclein predicts cognitive decline in Parkinson’s disease. J Neurol Neurosurg Psychiatry 88:818–824. https://doi.org/10.1136/jnnp-2016-314857
Lippa CF, Schmidt ML, Lee VM, Trojanowski JQ (1999) Antibodies to alpha-synuclein detect Lewy bodies in many Down’s syndrome brains with Alzheimer’s disease. Ann Neurol 45:353–357
Lista S, Emanuele E (2011) Role of amyloid beta1-42 and neuroimaging biomarkers in Alzheimer’s disease. Biomark Med 5:411–413. https://doi.org/10.2217/bmm.11.50
Lista S, Faltraco F, Hampel H (2013) Biological and methodical challenges of blood-based proteomics in the field of neurological research. Prog Neurobiol 101–102:18–34. https://doi.org/10.1016/j.pneurobio.2012.06.006
Lista S, Faltraco F, Prvulovic D, Hampel H (2013) Blood and plasma-based proteomic biomarker research in Alzheimer’s disease. Prog Neurobiol 101–102:1–17. https://doi.org/10.1016/j.pneurobio.2012.06.007
Lista S, Garaci FG, Ewers M, Teipel S, Zetterberg H, Blennow K et al (2014) CSF Abeta1-42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer’s disease. Alzheimers Dement 10:381–392. https://doi.org/10.1016/j.jalz.2013.04.506
Lista S, Hampel H (2017) Synaptic degeneration and neurogranin in the pathophysiology of Alzheimer’s disease. Expert Rev Neurother 17:47–57. https://doi.org/10.1080/14737175.2016.1204234
Lista S, Khachaturian ZS, Rujescu D, Garaci F, Dubois B, Hampel H (2016) Application of systems theory in longitudinal studies on the origin and progression of Alzheimer’s disease. Methods Mol Biol 1303:49–67. https://doi.org/10.1007/978-1-4939-2627-5_2
Lista S, Toschi N, Baldacci F, Zetterberg H, Blennow K, Kilimann I et al (2017) Diagnostic accuracy of CSF neurofilament light chain protein in the biomarker-guided classification system for Alzheimer’s disease. Neurochem Int 108:355–360. https://doi.org/10.1016/j.neuint.2017.05.010
Lista S, Toschi N, Baldacci F, Zetterberg H, Blennow K, Kilimann I et al (2017) Cerebrospinal fluid neurogranin as a biomarker of neurodegenerative diseases: a cross-sectional study. J Alzheimers Dis 59:1327–1334. https://doi.org/10.3233/jad-170368
Lista S, Zetterberg H, O’Bryant SE, Blennow K, Hampel H (2017) Evolving relevance of neuroproteomics in Alzheimer’s disease. Methods Mol Biol 1598:101–115. https://doi.org/10.1007/978-1-4939-6952-4_5
Liu M, Guo S, Hibbert JM, Jain V, Singh N, Wilson NO et al (2011) CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev 22:121–130. https://doi.org/10.1016/j.cytogfr.2011.06.001
Ljungqvist J, Zetterberg H, Mitsis M, Blennow K, Skoglund T (2017) Serum neurofilament light protein as a marker for diffuse axonal injury: results from a case series study. J Neurotrauma 34:1124–1127. https://doi.org/10.1089/neu.2016.4496
Llorens F, Kruse N, Karch A, Schmitz M, Zafar S, Gotzmann N et al (2017) Validation of α-synuclein as a CSF biomarker for sporadic Creutzfeldt-Jakob disease. Mol Neurobiol 55:2249–2257. https://doi.org/10.1007/s12035-017-0479-5
Loeffler DA, Connor JR, Juneau PL, Snyder BS, Kanaley L, DeMaggio AJ et al (1995) Transferrin and iron in normal, Alzheimer’s disease, and Parkinson’s disease brain regions. J Neurochem 65:710–724
Lövheim H, Elgh F, Johansson A, Zetterberg H, Blennow K, Hallmans G et al (2017) Plasma concentrations of free amyloid β cannot predict the development of Alzheimer’s disease. Alzheimers Dement 13:778–782. https://doi.org/10.1016/j.jalz.2016.12.004
Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N et al (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84:2247–2257. https://doi.org/10.1212/WNL.0000000000001642
Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ et al (2012) Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338:949–953. https://doi.org/10.1126/science.1227157
Luo X, Hou L, Shi H, Zhong X, Zhang Y, Zheng D et al (2013) CSF levels of the neuronal injury biomarker visinin-like protein-1 in Alzheimer’s disease and dementia with Lewy bodies. J Neurochem 127:681–690. https://doi.org/10.1111/jnc.12331
Lycke JN, Karlsson JE, Andersen O, Rosengren LE (1998) Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 64:402–404
Majbour NK, Chiasserini D, Vaikath NN, Eusebi P, Tokuda T, van de Berg W et al (2017) Increased levels of CSF total but not oligomeric or phosphorylated forms of alpha-synuclein in patients diagnosed with probable Alzheimer’s disease. Sci Rep 7:40263. https://doi.org/10.1038/srep40263
Majbour NK, Vaikath NN, van Dijk KD, Ardah MT, Varghese S, Vesterager LB et al (2016) Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease. Mol Neurodegener 11:7. https://doi.org/10.1186/s13024-016-0072-9
Marsh SE, Blurton-Jones M (2012) Examining the mechanisms that link β-amyloid and α-synuclein pathologies. Alzheimers Res Ther 4:11. https://doi.org/10.1186/alzrt109
Masliah E, Hansen L, Albright T, Mallory M, Terry RD (1991) Immunoelectron microscopic study of synaptic pathology in Alzheimer’s disease. Acta Neuropathol 81:428–433
Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW Jr et al (2001) Altered expression of synaptic proteins occurs early during progression of Alzheimer’s disease. Neurology 56:127–129
Masliah E, Terry RD, Alford M, DeTeresa R, Hansen LA (1991) Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer’s disease. Am J Pathol 138:235–246
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL (2015) Alzheimer’s disease. Nat Rev Dis Primers 1:15056. https://doi.org/10.1038/nrdp.2015.56
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249
Mattsson N, Andreasson U, Zetterberg H, Blennow K, Alzheimer’s Disease Neuroimaging Initiative (2017) Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 74:557–566. https://doi.org/10.1001/jamaneurol.2016.6117
Mattsson N, Carrillo MC, Dean RA, Devous MD Sr, Nikolcheva T, Pesini P et al (2015) Revolutionizing Alzheimer’s disease and clinical trials through biomarkers. Alzheimers Dement (Amst) 1:412–419. https://doi.org/10.1016/j.dadm.2015.09.001
Mattsson N, Insel PS, Palmqvist S, Portelius E, Zetterberg H, Weiner M et al (2016) Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer’s disease. EMBO Mol Med 8:1184–1196. https://doi.org/10.15252/emmm.201606540
Mattsson N, Insel PS, Palmqvist S, Stomrud E, van Westen D, Minthon L et al (2016) Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis. Nat Commun 7:10918. https://doi.org/10.1038/ncomms10918
Mattsson N, Tabatabaei S, Johansson P, Hansson O, Andreasson U, Månsson JE et al (2011) Cerebrospinal fluid microglial markers in Alzheimer’s disease: elevated chitotriosidase activity but lack of diagnostic utility. Neuromol Med 13:151–159. https://doi.org/10.1007/s12017-011-8147-9
Mattsson N, Zetterberg H, Janelidze S, Insel PS, Andreasson U, Stomrud E et al (2016) Plasma tau in Alzheimer disease. Neurology 87:1827–1835. https://doi.org/10.1212/WNL.0000000000003246
McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C et al (2005) Aβ42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47:191–199. https://doi.org/10.1016/j.neuron.2005.06.030
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269. https://doi.org/10.1016/j.jalz.2011.03.005
Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM (2000) Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease. Arch Neurol 57:100–105
Mellergård J, Tisell A, Blystad I, Grönqvist A, Blennow K, Olsson B et al (2017) Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis. Eur J Neurol 24:112–121. https://doi.org/10.1111/ene.13162
Meredith JE Jr, Sankaranarayanan S, Guss V, Lanzetti AJ, Berisha F, Neely RJ et al (2013) Characterization of novel CSF tau and ptau biomarkers for Alzheimer’s disease. PLoS One 8:e76523. https://doi.org/10.1371/journal.pone.0076523
Mielke MM, Hagen CE, Wennberg AMV, Airey DC, Savica R, Knopman DS et al (2017) Association of plasma total tau level with cognitive decline and risk of mild cognitive impairment or dementia in the Mayo Clinic Study on Aging. JAMA Neurol 74:1073–1080. https://doi.org/10.1001/jamaneurol.2017.1359
Mohorko N, Bresjanac M (2008) Tau protein and human tauopathies: an overview. Zdrav Vestn 77:II-35-41
Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I et al (2008) Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 213:315–325. https://doi.org/10.1016/j.expneurol.2008.06.004
Mollenhauer B, Steinacker P, Bahn E, Bibl M, Brechlin P, Schlossmacher MG et al (2007) Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: marker candidates for dementia with Lewy bodies. Neurodegener Dis 4:366–375. https://doi.org/10.1159/000105157
Mori Y, Yoshino Y, Ochi S, Yamazaki K, Kawabe K, Abe M et al (2015) TREM2 mRNA expression in leukocytes is increased in Alzheimer’s disease and schizophrenia. PLoS One 10:e0136835. https://doi.org/10.1371/journal.pone.0136835
Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D et al (1995) Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 38:643–648. https://doi.org/10.1002/ana.410380413
Mroczko B, Groblewska M, Zboch M, Muszynski P, Zajkowska A, Borawska R et al (2015) Evaluation of visinin-like protein 1 concentrations in the cerebrospinal fluid of patients with mild cognitive impairment as a dynamic biomarker of Alzheimer’s disease. J Alzheimers Dis 43:1031–1037. https://doi.org/10.3233/jad-141050
Mulder SD, van der Flier WM, Verheijen JH, Mulder C, Scheltens P, Blankenstein MA et al (2010) BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology. J Alzheimers Dis 20:253–260. https://doi.org/10.3233/jad-2010-1367
Mulugeta E, Londos E, Ballard C, Alves G, Zetterberg H, Blennow K et al (2011) CSF amyloid β38 as a novel diagnostic marker for dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 82:160–164. https://doi.org/10.1136/jnnp.2009.199398
Naj AC, Schellenberg GD, Alzheimer’s Disease Genetics Consortium (2017) Genomic variants, genes, and pathways of Alzheimer’s disease: an overview. Am J Med Genet B Neuropsychiatr Genet 174:5–26. https://doi.org/10.1002/ajmg.b.32499
Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Doré V et al (2018) High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature 554:249–254. https://doi.org/10.1038/nature25456
Nath S, Koziarz A, Badhiwala JH, Alhazzani W, Jaeschke R, Sharma S et al (2017) Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. Lancet 391:1197–1204. https://doi.org/10.1016/S0140-6736(17)32451-0
Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ et al (2012) Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 71:362–381. https://doi.org/10.1097/NEN.0b013e31825018f7
Neumann K, Farías G, Slachevsky A, Perez P, Maccioni RB (2011) Human platelets tau: a potential peripheral marker for Alzheimer’s disease. J Alzheimers Dis 25:103–109. https://doi.org/10.3233/JAD-2011-101641
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. https://doi.org/10.1126/science.1134108
Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, Malmeström C et al (2017) Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis. J Neurochem 141:296–304. https://doi.org/10.1111/jnc.13881
Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, Malmeström C et al (2017) Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis. Mult Scler 23:62–71. https://doi.org/10.1177/1352458516639384
O’Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Lista S et al (2015) Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer’s disease research. Alzheimers Dement 11:549–560. https://doi.org/10.1016/j.jalz.2014.08.099
O’Bryant SE, Mielke MM, Rissman RA, Lista S, Vanderstichele H, Zetterberg H et al (2017) Blood-based biomarkers in Alzheimer disease: current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement 13:45–58. https://doi.org/10.1016/j.jalz.2016.09.014
Öhrfelt A, Brinkmalm A, Dumurgier J, Brinkmalm G, Hansson O, Zetterberg H et al (2016) The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease. Alzheimers Res Ther 8:41. https://doi.org/10.1186/s13195-016-0208-8
Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 15:673–684. https://doi.org/10.1016/s1474-4422(16)00070-3
Olsson F, Schmidt S, Althoff V, Munter LM, Jin S, Rosqvist S et al (2014) Characterization of intermediate steps in amyloid beta (Aβ) production under near-native conditions. J Biol Chem 289:1540–1550. https://doi.org/10.1074/jbc.M113.498246
Ovod V, Ramsey KN, Mawuenyega KG, Bollinger JG, Hicks T, Schneider T et al (2017) Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841–849. https://doi.org/10.1016/j.jalz.2017.06.2266
Palmqvist S, Janelidze S, Stromrud E, Zetterberg H, Karl J, Mattsson N et al (2018) Detecting brain amyloid status using fully automated plasma Aβ biomarker assays. Abstract presented at the Alzheimer’s Association International Conference (AAIC) 2018. Chicago (22–26 July 2018)
Palmqvist S, Zetterberg H, Mattsson N, Johansson P, Alzheimer’s Disease Neuroimaging Initiative, Minthon L et al (2015) Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology 85:1240–1249. https://doi.org/10.1212/wnl.0000000000001991
Pannee J, Portelius E, Minthon L, Gobom J, Andreasson U, Zetterberg H et al (2016) Reference measurement procedure for CSF amyloid beta (Aβ)1-42 and the CSF Aβ1-42/Aβ1-40 ratio—a cross-validation study against amyloid PET. J Neurochem 139:651–658. https://doi.org/10.1111/jnc.13838
Pannee J, Törnqvist U, Westerlund A, Ingelsson M, Lannfelt L, Brinkmalm G et al (2014) The amyloid-β degradation pattern in plasma—a possible tool for clinical trials in Alzheimer’s disease. Neurosci Lett 573:7–12. https://doi.org/10.1016/j.neulet.2014.04.041
Park JC, Han SH, Cho HJ, Byun MS, Yi D, Choe YM et al (2017) Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition. Alzheimers Res Ther 9:20. https://doi.org/10.1186/s13195-017-0248-8
Parnetti L, Eusebi P, Lleó A (2016) Cerebrospinal fluid biomarkers for target engagement and efficacy in clinical trials for Alzheimer’s and Parkinson’s diseases. Front Neurol Neurosci 39:117–123. https://doi.org/10.1159/000445452
Pascoal TA, Mathotaarachchi S, Shin M, Benedet AL, Mohades S, Wang S et al (2017) Synergistic interaction between amyloid and tau predicts the progression to dementia. Alzheimers Dement 13:644–653. https://doi.org/10.1016/j.jalz.2016.11.005
Pereira JB, Strandberg TO, Palmqvist S, Volpe G, van Westen D, Westman E et al (2018) Amyloid network topology characterizes the progression of Alzheimer’s disease during the predementia stages. Cereb Cortex 28:340–349. https://doi.org/10.1093/cercor/bhx294
Pereira JB, Westman E, Hansson O, Alzheimer’s Disease Neuroimaging Initiative (2017) Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer’s disease. Neurobiol Aging 58:14–29. https://doi.org/10.1016/j.neurobiolaging.2017.06.002
Perneczky R, Alexopoulos P, Alzheimer’s Disease Neuroimaging Initiative (2014) Cerebrospinal fluid BACE1 activity and markers of amyloid precursor protein metabolism and axonal degeneration in Alzheimer’s disease. Alzheimers Dement 10:S425–S429 e421. https://doi.org/10.1016/j.jalz.2013.09.006
Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele H, Zorzi W et al (2012) Risk of Alzheimer’s disease biological misdiagnosis linked to cerebrospinal collection tubes. J Alzheimers Dis 31:13–20. https://doi.org/10.3233/JAD-2012-120361
Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS et al (2013) Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol 74:199–208. https://doi.org/10.1002/ana.23931
Petzold A, Keir G, Warren J, Fox N, Rossor MN (2007) A systematic review and meta-analysis of CSF neurofilament protein levels as biomarkers in dementia. Neurodegener Dis 4:185–194. https://doi.org/10.1159/000101843
Piccio L, Deming Y, Del-Águila JL, Ghezzi L, Holtzman DM, Fagan AM et al (2016) Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol 131:925–933. https://doi.org/10.1007/s00401-016-1533-5
Pijnenburg YA, Janssen JC, Schoonenboom NS, Petzold A, Mulder C, Stigbrand T et al (2007) CSF neurofilaments in frontotemporal dementia compared with early onset Alzheimer’s disease and controls. Dement Geriatr Cogn Disord 23:225–230. https://doi.org/10.1159/000099473
Portelius E, Price E, Brinkmalm G, Stiteler M, Olsson M, Persson R et al (2011) A novel pathway for amyloid precursor protein processing. Neurobiol Aging 32:1090–1098. https://doi.org/10.1016/j.neurobiolaging.2009.06.002
Portelius E, Westman-Brinkmalm A, Zetterberg H, Blennow K (2006) Determination of β-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. J Proteome Res 5:1010–1016. https://doi.org/10.1021/pr050475v
Portelius E, Zetterberg H, Skillback T, Tornqvist U, Andreasson U, Trojanowski JQ et al (2015) Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer’s disease. Brain 138:3373–3385. https://doi.org/10.1093/brain/awv267
Pottiez G, Yang L, Stewart T, Song N, Aro P, Galasko DR et al (2017) Mass-spectrometry-based method to quantify in parallel tau and amyloid beta 1-42 in CSF for the diagnosis of Alzheimer’s disease. J Proteome Res 16:1228–1238. https://doi.org/10.1021/acs.jproteome.6b00829
Querol-Vilaseca M, Colom-Cadena M, Pegueroles J, San Martín-Paniello C, Clarimon J, Belbin O et al (2017) YKL-40 (Chitinase 3-like I) is expressed in a subset of astrocytes in Alzheimer’s disease and other tauopathies. J Neuroinflammation 14:118. https://doi.org/10.1186/s12974-017-0893-7
Racine AM, Koscik RL, Nicholas CR, Clark LR, Okonkwo OC, Oh JM et al (2016) Cerebrospinal fluid ratios with Aβ42 predict preclinical brain β-amyloid accumulation. Alzheimers Dement (Amst) 2:27–38. https://doi.org/10.1016/j.dadm.2015.11.006
Reiman EM (2017) Alzheimer disease in 2016: putting AD treatments and biomarkers to the test. Nat Rev Neurol 13:74–76. https://doi.org/10.1038/nrneurol.2017.1
Rhodin JA, Thomas T (2001) A vascular connection to Alzheimer’s disease. Microcirculation 8:207–220. https://doi.org/10.1038/sj/mn/7800086
Riemenschneider M, Wagenpfeil S, Vanderstichele H, Otto M, Wiltfang J, Kretzschmar H et al (2003) Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias. Mol Psychiatry 8:343–347. https://doi.org/10.1038/sj.mp.4001220
Ritter A, Cummings J (2015) Fluid biomarkers in clinical trials of Alzheimer’s disease therapeutics. Front Neurol 6:186. https://doi.org/10.3389/fneur.2015.00186
Rivero-Santana A, Ferreira D, Perestelo-Pérez L, Westman E, Wahlund LO, Sarría A et al (2017) Cerebrospinal fluid biomarkers for the differential diagnosis between Alzheimer’s disease and frontotemporal lobar degeneration: systematic review, HSROC analysis, and confounding factors. J Alzheimers Dis 55:625–644. https://doi.org/10.3233/JAD-160366
Robinson J, Lee E, Xie S, Rennert L, Suh E, Bredenberg C et al (2018) Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain 141:2181–2193. https://doi.org/10.1093/brain/awy146
Roe CM, Fagan AM, Grant EA, Hassenstab J, Moulder KL, Maue Dreyfus D et al (2013) Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Neurology 80:1784–1791. https://doi.org/10.1212/WNL.0b013e3182918ca6
Rojas JC, Karydas A, Bang J, Tsai RM, Blennow K, Liman V et al (2016) Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol 3:216–225. https://doi.org/10.1002/acn3.290
Rosén C, Andersson CH, Andreasson U, Molinuevo JL, Bjerke M, Rami L et al (2014) Increased levels of chitotriosidase and YKL-40 in cerebrospinal fluid from patients with Alzheimer’s disease. Dement Geriatr Cogn Dis Extra 4:297–304. https://doi.org/10.1159/000362164
Roussos P, Katsel P, Fam P, Tan W, Purohit DP, Haroutunian V (2015) The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer’s dementia. Alzheimers Dement 11:1163–1170. https://doi.org/10.1016/j.jalz.2014.10.013
Rowe CC, Bourgeat P, Ellis KA, Brown B, Lim YY, Mulligan R et al (2013) Predicting Alzheimer disease with β-amyloid imaging: results from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing. Ann Neurol 74:905–913. https://doi.org/10.1002/ana.24040
Russell CL, Mitra V, Hansson K, Blennow K, Gobom J, Zetterberg H et al (2017) Comprehensive quantitative profiling of tau and phosphorylated tau peptides in cerebrospinal fluid by mass spectrometry provides new biomarker candidates. J Alzheimers Dis 55:303–313. https://doi.org/10.3233/JAD-160633
Salminen A, Kauppinen A, Kaarniranta K (2017) Hypoxia/ischemia activate processing of amyloid precursor protein: impact of vascular dysfunction in the pathogenesis of Alzheimer’s disease. J Neurochem 140:536–549. https://doi.org/10.1111/jnc.13932
Salvadores N, Shahnawaz M, Scarpini E, Tagliavini F, Soto C (2014) Detection of misfolded Aβ oligomers for sensitive biochemical diagnosis of Alzheimer’s disease. Cell Rep 7:261–268. https://doi.org/10.1016/j.celrep.2014.02.031
Sanabria-Castro A, Alvarado-Echeverría I, Monge-Bonilla C (2017) Molecular pathogenesis of Alzheimer’s disease: an update. Ann Neurosci 24:46–54. https://doi.org/10.1159/000464422
Sanfilippo C, Forlenza O, Zetterberg H, Blennow K (2016) Increased neurogranin concentrations in cerebrospinal fluid of Alzheimer’s disease and in mild cognitive impairment due to AD. J Neural Transm (Vienna) 123:1443–1447. https://doi.org/10.1007/s00702-016-1597-3
Savage MJ, Holder DJ, Wu G, Kaplow J, Siuciak JA, Potter WZ (2015) Soluble BACE-1 activity and sAβPPβ concentrations in Alzheimer’s disease and age-matched healthy control cerebrospinal fluid from the Alzheimer’s Disease Neuroimaging Initiative-1 baseline cohort. J Alzheimers Dis 46:431–440. https://doi.org/10.3233/jad-142778
Savage MJ, Kalinina J, Wolfe A, Tugusheva K, Korn R, Cash-Mason T et al (2014) A sensitive aβ oligomer assay discriminates Alzheimer’s and aged control cerebrospinal fluid. J Neurosci 34:2884–2897. https://doi.org/10.1523/JNEUROSCI.1675-13.2014
Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27:1372–1384. https://doi.org/10.1016/j.neurobiolaging.2005.09.012
Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S et al (2016) Alzheimer’s disease. Lancet 388:505–517. https://doi.org/10.1016/s0140-6736(15)01124-1
Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N et al (1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 2:864–870
Schmidt ML, Murray J, Lee VM, Hill WD, Wertkin A, Trojanowski JQ (1991) Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. Am J Pathol 139:53–65
Schneider LS, Mangialasche F, Andreasen N, Feldman H, Giacobini E, Jones R et al (2014) Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014. J Intern Med 275:251–283. https://doi.org/10.1111/joim.12191
Schuster J, Funke SA (2016) Methods for the specific detection and quantitation of amyloid-β oligomers in cerebrospinal fluid. J Alzheimers Dis 53:53–67. https://doi.org/10.3233/JAD-151029
Seeburger JL, Holder DJ, Combrinck M, Joachim C, Laterza O, Tanen M et al (2015) Cerebrospinal fluid biomarkers distinguish postmortem-confirmed Alzheimer’s disease from other dementias and healthy controls in the OPTIMA cohort. J Alzheimers Dis 44:525–539. https://doi.org/10.3233/JAD-141725
Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8:595–608. https://doi.org/10.15252/emmm.201606210
Sengupta U, Nilson AN, Kayed R (2016) The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine 6:42–49. https://doi.org/10.1016/j.ebiom.2016.03.035
Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D et al (1992) Isolation and quantification of soluble Alzheimer’s β-peptide from biological fluids. Nature 359:325–327. https://doi.org/10.1038/359325a0
Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M et al (2016) The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature 537:50–56. https://doi.org/10.1038/nature19323
Shahim P, Zetterberg H, Tegner Y, Blennow K (2017) Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology 88:1788–1794. https://doi.org/10.1212/wnl.0000000000003912
Shahnawaz M, Tokuda T, Waragai M, Mendez N, Ishii R, Trenkwalder C et al (2017) Development of a biochemical diagnosis of Parkinson disease by detection of α-synuclein misfolded aggregates in cerebrospinal fluid. JAMA Neurol 74:163–172. https://doi.org/10.1001/jamaneurol.2016.4547
Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC et al (2009) Cerebrospinal fluid biomarker signature in Alzheimer’s Disease neuroimaging initiative subjects. Ann Neurol 65:403–413. https://doi.org/10.1002/ana.21610
Shaw LM, Vanderstichele H, Knapik-Czajka M, Figurski M, Coart E, Blennow K et al (2011) Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI. Acta Neuropathol 121:597–609. https://doi.org/10.1007/s00401-011-0808-0
Sheinerman KS, Toledo JB, Tsivinsky VG, Irwin D, Grossman M, Weintraub D et al (2017) Circulating brain-enriched microRNAs as novel biomarkers for detection and differentiation of neurodegenerative diseases. Alzheimers Res Ther 9:89. https://doi.org/10.1186/s13195-017-0316-0
Shekhar S, Kumar R, Rai N, Kumar V, Singh K, Upadhyay AD et al (2016) Estimation of tau and phosphorylated tau181 in serum of Alzheimer’s disease and mild cognitive impairment patients. PLoS One 11:e0159099. https://doi.org/10.1371/journal.pone.0159099
Shen Y, Wang H, Sun Q, Yao H, Keegan AP, Mullan M et al (2018) Increased plasma beta-secretase 1 may predict conversion to Alzheimer’s disease dementia in individuals with mild cognitive impairment. Biol Psychiatry 83:447–455. https://doi.org/10.1016/j.biopsych.2017.02.007
Shi M, Zabetian CP, Hancock AM, Ginghina C, Hong Z, Yearout D et al (2010) Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson’s disease. Neurosci Lett 480:78–82. https://doi.org/10.1016/j.neulet.2010.06.009
Sims R, van der Lee SJ, Naj AC, Bellenguez C, Badarinarayan N, Jakobsdottir J et al (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet 49:1373–1384. https://doi.org/10.1038/ng.3916
Singh N, Haldar S, Tripathi AK, Horback K, Wong J, Sharma D et al (2014) Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxid Redox Signal 20:1324–1363. https://doi.org/10.1089/ars.2012.4931
Sjögren M, Blomberg M, Jonsson M, Wahlund LO, Edman A, Lind K et al (2001) Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 66:510–516. https://doi.org/10.1002/jnr.1242
Skillbäck T, Farahmand B, Bartlett JW, Rosén C, Mattsson N, Nägga K et al (2014) CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology 83:1945–1953. https://doi.org/10.1212/wnl.0000000000001015
Skillbäck T, Rosén C, Asztely F, Mattsson N, Blennow K, Zetterberg H (2014) Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt-Jakob disease: results from the Swedish Mortality Registry. JAMA Neurol 71:476–483. https://doi.org/10.1001/jamaneurol.2013.6455
Slachevsky A, Guzmán-Martínez L, Delgado C, Reyes P, Farías GA, Muñoz-Neira C et al (2017) Tau platelets correlate with regional brain atrophy in patients with Alzheimer’s disease. J Alzheimers Dis 55:1595–1603. https://doi.org/10.3233/JAD-160652
Slaets S, Le Bastard N, Martin JJ, Sleegers K, Van Broeckhoven C, De Deyn PP et al (2013) Cerebrospinal fluid Aβ1-40 improves differential dementia diagnosis in patients with intermediate p-tau181 levels. J Alzheimers Dis 36:759–767. https://doi.org/10.3233/jad-130107
Slaets S, Vanmechelen E, Le Bastard N, Decraemer H, Vandijck M, Martin JJ et al (2014) Increased CSF α-synuclein levels in Alzheimer’s disease: correlation with tau levels. Alzheimers Dement 10:S290–S298. https://doi.org/10.1016/j.jalz.2013.10.004
Snyder HM, Corriveau RA, Craft S, Faber JE, Greenberg SM, Knopman D et al (2015) Vascular contributions to cognitive impairment and dementia including Alzheimer’s disease. Alzheimers Dement 11:710–717. https://doi.org/10.1016/j.jalz.2014.10.008
Soares HD, Gasior M, Toyn JH, Wang JS, Hong Q, Berisha F et al (2016) The γ-secretase modulator, BMS-932481, modulates Aβ peptides in the plasma and cerebrospinal fluid of healthy volunteers. J Pharmacol Exp Ther 358:138–150. https://doi.org/10.1124/jpet.116.232256
Steardo L Jr, Bronzuoli MR, Iacomino A, Esposito G, Steardo L, Scuderi C (2015) Does neuroinflammation turn on the flame in Alzheimer’s disease? Focus on astrocytes. Front Neurosci 9:259. https://doi.org/10.3389/fnins.2015.00259
Strozyk D, Blennow K, White LR, Launer LJ (2003) CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60:652–656
Suárez-Calvet M, Araque Caballero MÁ, Kleinberger G, Bateman RJ, Fagan AM, Morris JC et al (2016) Early changes in CSF sTREM2 in dominantly inherited Alzheimer’s disease occur after amyloid deposition and neuronal injury. Sci Transl Med 8:369ra178. https://doi.org/10.1126/scitranslmed.aag1767
Suárez-Calvet M, Dols-Icardo O, Lladó A, Sánchez-Valle R, Hernández I, Amer G et al (2014) Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation. J Neurol Neurosurg Psychiatry 85:684–691. https://doi.org/10.1136/jnnp-2013-305972
Suárez-Calvet M, Kleinberger G, Araque Caballero MÁ, Brendel M, Rominger A, Alcolea D et al (2016) sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer’s disease and associate with neuronal injury markers. EMBO Mol Med 8:466–476. https://doi.org/10.15252/emmm.201506123
Sutphen CL, McCue L, Herries EM, Xiong C, Ladenson JH, Holtzman DM et al (2018) Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer’s disease. Alzheimers Dement 14:869–879. https://doi.org/10.1016/j.jalz.2018.01.012
Suzuki N, Cheung TT, Cai XD, Odaka A, Otvos L Jr, Eckman C et al (1994) An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 264:1336–1340
Suzuki N, Iwatsubo T, Odaka A, Ishibashi Y, Kitada C, Ihara Y (1994) High tissue content of soluble beta 1-40 is linked to cerebral amyloid angiopathy. Am J Pathol 145:452–460
Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010) A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 68:930–941. https://doi.org/10.1016/j.biopsych.2010.06.012
Sze CI, Bi H, Kleinschmidt-DeMasters BK, Filley CM, Martin LJ (2000) Selective regional loss of exocytotic presynaptic vesicle proteins in Alzheimer’s disease brains. J Neurol Sci 175:81–90
Tan YJ, Ng ASL, Vipin A, Lim JKW, Chander RJ, Ji F et al (2017) Higher peripheral TREM2 mRNA levels relate to cognitive deficits and hippocampal atrophy in Alzheimer’s disease and amnestic mild cognitive impairment. J Alzheimers Dis 58:413–423. https://doi.org/10.3233/JAD-161277
Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H et al (2009) Cerebrospinal fluid β-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66:382–389. https://doi.org/10.1001/archneurol.2008.596
Tarawneh R, D’Angelo G, Crimmins D, Herries E, Griest T, Fagan AM et al (2016) Diagnostic and prognostic utility of the synaptic marker neurogranin in Alzheimer disease. JAMA Neurol 73:561–571. https://doi.org/10.1001/jamaneurol.2016.0086
Tarawneh R, D’Angelo G, Macy E, Xiong C, Carter D, Cairns NJ et al (2011) Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease. Ann Neurol 70:274–285. https://doi.org/10.1002/ana.22448
Tarawneh R, Head D, Allison S, Buckles V, Fagan AM, Ladenson JH (2015) Cerebrospinal fluid markers of neurodegeneration and rates of brain atrophy in early Alzheimer disease. JAMA Neurol 72:656–665. https://doi.org/10.1001/jamaneurol.2015.0202
Tarawneh R, Lee JM, Ladenson JH, Morris JC, Holtzman DM (2012) CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease. Neurology 78:709–719. https://doi.org/10.1212/WNL.0b013e318248e568
Tatebe H, Kasai T, Ohmichi T, Kishi Y, Kakeya T, Waragai M et al (2017) Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome. Mol Neurodegener 12:63. https://doi.org/10.1186/s13024-017-0206-8
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580. https://doi.org/10.1002/ana.410300410
The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group (1998) Consensus report of the working group on: “Molecular and biochemical markers of Alzheimer’s disease”. Neurobiol Aging 19:109–116
Thorsell A, Bjerke M, Gobom J, Brunhage E, Vanmechelen E, Andreasen N et al (2010) Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer’s disease. Brain Res 1362:13–22. https://doi.org/10.1016/j.brainres.2010.09.073
Timmers M, Barão S, Van Broeck B, Tesseur I, Slemmon J, De Waepenaert K et al (2017) BACE1 dynamics upon inhibition with a BACE inhibitor and correlation to downstream Alzheimer’s disease markers in elderly healthy participants. J Alzheimers Dis 56:1437–1449. https://doi.org/10.3233/JAD-160829
Tirucherai G, Ahlijanian M, Crowell J, Kolaitis G, Skudalski S, Medlock M (2016) A single ascending dose study of the tau-directed monoclonal antibody BMS-986168. Abstract presented at the 20th International Congress of Parkinson’s Disease and Movement Disorders. Berlin (19–23 June 2016)
Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T et al (2010) Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 75:1766–1772. https://doi.org/10.1212/WNL.0b013e3181fd613b
Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M et al (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 136:2697–2706. https://doi.org/10.1093/brain/awt188
Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J (2013) CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and Abeta in Alzheimer’s disease. Acta Neuropathol 126:683–697. https://doi.org/10.1007/s00401-013-1148-z
Toledo JB, Xie SX, Trojanowski JQ, Shaw LM (2013) Longitudinal change in CSF tau and Aβ biomarkers for up to 48 months in ADNI. Acta Neuropathol 126:659–670. https://doi.org/10.1007/s00401-013-1151-4
Toombs J, Paterson RW, Lunn MP, Nicholas JM, Fox NC, Chapman MD et al (2013) Identification of an important potential confound in CSF AD studies: aliquot volume. Clin Chem Lab Med 51:2311–2317. https://doi.org/10.1515/cclm-2013-0293
Tu S, Okamoto S, Lipton SA, Xu H (2014) Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease. Mol Neurodegener 9:48. https://doi.org/10.1186/1750-1326-9-48
Tyson T, Steiner JA, Brundin P (2016) Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology. J Neurochem 139(Suppl 1):275–289. https://doi.org/10.1111/jnc.13449
Tzen KY, Yang SY, Chen TF, Cheng TW, Horng HE, Wen HP et al (2014) Plasma Aβ but not tau is related to brain PiB retention in early Alzheimer’s disease. ACS Chem Neurosci 5:830–836. https://doi.org/10.1021/cn500101j
van Bergen JM, Li X, Hua J, Schreiner SJ, Steininger SC, Quevenco FC et al (2016) Colocalization of cerebral iron with amyloid beta in mild cognitive impairment. Sci Rep 6:35514. https://doi.org/10.1038/srep35514
van Oijen M, Hofman A, Soares HD, Koudstaal PJ, Breteler MM (2006) Plasma Aβ(1-40) and Aβ(1-42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol 5:655–660. https://doi.org/10.1016/S1474-4422(06)70501-4
van Rossum IA, Vos S, Handels R, Visser PJ (2010) Biomarkers as predictors for conversion from mild cognitive impairment to Alzheimer-type dementia: implications for trial design. J Alzheimers Dis 20:881–891. https://doi.org/10.3233/JAD-2010-091606
Vanderstichele H, Bibl M, Engelborghs S, Le Bastard N, Lewczuk P, Molinuevo JL et al (2012) Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer’s disease diagnosis: a consensus paper from the Alzheimer’s Biomarkers Standardization Initiative. Alzheimers Dement 8:65–73. https://doi.org/10.1016/j.jalz.2011.07.004
Vassar R, Kuhn PH, Haass C, Kennedy ME, Rajendran L, Wong PC et al (2014) Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J Neurochem 130:4–28. https://doi.org/10.1111/jnc.12715
Verberk IMW, Slot RE, Verfaillie SCJ, Heijst H, Prins ND, van Berckel BNM et al (2018) Plasma amyloid as prescreener for the earliest Alzheimer pathological changes. Ann Neurol. https://doi.org/10.1002/ana.25334
Vickers JC, Riederer BM, Marugg RA, Buee-Scherrer V, Buee L, Delacourte A et al (1994) Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer’s disease. Neuroscience 62:1–13
Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O et al (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 12:357–367. https://doi.org/10.1016/S1474-4422(13)70044-9
Vivacqua G, Latorre A, Suppa A, Nardi M, Pietracupa S, Mancinelli R et al (2016) Abnormal salivary total and oligomeric alpha-synuclein in Parkinson’s disease. PLoS One 11:e0151156. https://doi.org/10.1371/journal.pone.0151156
Wang MJ, Yi S, Han JY, Park SY, Jang JW, Chun IK et al (2017) Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease. Alzheimers Res Ther 9:98. https://doi.org/10.1186/s13195-017-0324-0
Wang Y, Shi M, Chung KA, Zabetian CP, Leverenz JB, Berg D et al (2012) Phosphorylated α-synuclein in Parkinson’s disease. Sci Transl Med 4:121ra120. https://doi.org/10.1126/scitranslmed.3002566
Waragai M, Yoshida M, Mizoi M, Saiki R, Kashiwagi K, Takagi K et al (2012) Increased protein-conjugated acrolein and amyloid-β40/42 ratio in plasma of patients with mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 32:33–41. https://doi.org/10.3233/JAD-2012-120253
Wennström M, Surova Y, Hall S, Nilsson C, Minthon L, Hansson O et al (2015) The inflammatory marker YKL-40 is elevated in cerebrospinal fluid from patients with Alzheimer’s but not Parkinson’s disease or dementia with Lewy bodies. PLoS One 10:e0135458. https://doi.org/10.1371/journal.pone.0135458
Weston PSJ, Poole T, Ryan NS, Nair A, Liang Y, Macpherson K et al (2017) Serum neurofilament light in familial Alzheimer disease: a marker of early neurodegeneration. Neurology 89(21):2167–2175
Willemse E, van Uffelen K, Brix B, Engelborghs S, Vanderstichele H, Teunissen C (2017) How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ42/Aβ40 ratio. Alzheimers Dement 13:885–892. https://doi.org/10.1016/j.jalz.2017.01.010
Williams SM, Schulz P, Rosenberry TL, Caselli RJ, Sierks MR (2017) Blood-based oligomeric and other protein variant biomarkers to facilitate pre-symptomatic diagnosis and staging of Alzheimer’s disease. J Alzheimers Dis 58:23–35. https://doi.org/10.3233/jad-161116
Wiltfang J, Esselmann H, Bibl M, Hüll M, Hampel H, Kessler H et al (2007) Amyloid β peptide ratio 42/40 but not Aβ42 correlates with phospho-tau in patients with low- and high-CSF Aβ40 load. J Neurochem 101:1053–1059. https://doi.org/10.1111/j.1471-4159.2006.04404.x
Winston CN, Goetzl EJ, Akers JC, Carter BS, Rockenstein EM, Galasko D et al (2016) Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile. Alzheimers Dement (Amst) 3:63–72. https://doi.org/10.1016/j.dadm.2016.04.001
Wiseman FK, Al-Janabi T, Hardy J, Karmiloff-Smith A, Nizetic D, Tybulewicz VL et al (2015) A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neurosci 16:564–574. https://doi.org/10.1038/nrn3983
World Health Organization (2017) Dementia factsheet. http://www.who.int/mediacentre/factsheets/fs362/en/. Accessed August 2017
Wu G, Sankaranarayanan S, Tugusheva K, Kahana J, Seabrook G, Shi XP et al (2008) Decrease in age-adjusted cerebrospinal fluid β-secretase activity in Alzheimer’s subjects. Clin Biochem 41:986–996. https://doi.org/10.1016/j.clinbiochem.2008.04.022
Wu G, Sankaranarayanan S, Wong J, Tugusheva K, Michener MS, Shi X et al (2012) Characterization of plasma β-secretase (BACE1) activity and soluble amyloid precursor proteins as potential biomarkers for Alzheimer’s disease. J Neurosci Res 90:2247–2258. https://doi.org/10.1002/jnr.23122
Yan R (2017) Physiological functions of the β-site amyloid precursor protein cleaving enzyme 1 and 2. Front Mol Neurosci 10:97. https://doi.org/10.3389/fnmol.2017.00097
Yang CC, Chiu MJ, Chen TF, Chang HL, Liu BH, Yang SY (2018) Assay of plasma phosphorylated tau protein (threonine 181) and total tau protein in early-stage Alzheimer’s disease. J Alzheimers Dis 61:1323–1332. https://doi.org/10.3233/JAD-170810
Yang T, O’Malley TT, Kanmert D, Jerecic J, Zieske LR, Zetterberg H et al (2015) A highly sensitive novel immunoassay specifically detects low levels of soluble Abeta oligomers in human cerebrospinal fluid. Alzheimers Res Ther 7:14. https://doi.org/10.1186/s13195-015-0100-y
Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC et al (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337–351. https://doi.org/10.1016/j.neuron.2007.01.010
Yuan A, Rao MV, Veeranna Nixon RA (2012) Neurofilaments at a glance. J Cell Sci 125:3257–3263. https://doi.org/10.1242/jcs.104729
Yuan A, Rao MV, Veeranna Nixon RA (2017) Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harb Perspect Biol 9:a018309. https://doi.org/10.1101/cshperspect.a018309
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM et al (2016) TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron 92:252–264. https://doi.org/10.1016/j.neuron.2016.09.016
Zetterberg H, Andreasson U, Hansson O, Wu G, Sankaranarayanan S, Andersson ME et al (2008) Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol 65:1102–1107. https://doi.org/10.1001/archneur.65.8.1102
Zetterberg H, Pedersen M, Lind K, Svensson M, Rolstad S, Eckerström C et al (2007) Intra-individual stability of CSF biomarkers for Alzheimer’s disease over two years. J Alzheimers Dis 12:255–260
Zetterberg H, Skillbäck T, Mattsson N, Trojanowski JQ, Portelius E, Shaw LM et al (2016) Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol 73:60–67. https://doi.org/10.1001/jamaneurol.2015.3037
Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J et al (2013) Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther 5:9. https://doi.org/10.1186/alzrt163
Zhang B, Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak JS et al (2012) The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci 32:3601–3611. https://doi.org/10.1523/jneurosci.4922-11.2012
Zhang QS, Heng Y, Yuan YH, Chen NH (2017) Pathological α-synuclein exacerbates the progression of Parkinson’s disease through microglial activation. Toxicol Lett 265:30–37. https://doi.org/10.1016/j.toxlet.2016.11.002
Zhong Z, Ewers M, Teipel S, Bürger K, Wallin A, Blennow K et al (2007) Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. Arch Gen Psychiatry 64:718–726. https://doi.org/10.1001/archpsyc.64.6.718
Zhou W, Zhang J, Ye F, Xu G, Su H, Su Y et al (2017) Plasma neurofilament light chain levels in Alzheimer’s disease. Neurosci Lett 650:60–64. https://doi.org/10.1016/j.neulet.2017.04.027
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