Wimo A, Seeher K, Cataldi R, Cyhlarova E, Dielemann JL, Frisell O, et al. The worldwide costs of dementia in 2019. Alzheimer’s Dement. 2023;19:2865–73.

Article  Google Scholar 

Bali J, Gheinani AH, Zurbriggen S, Rajendran L. Role of genes linked to sporadic Alzheimer’s disease risk in the production of β-amyloid peptides. Proc Natl Acad Sci USA. 2012;109:15307–11.

Article  PubMed  PubMed Central  Google Scholar 

Cummings J, Aisen P, Lemere C, Atri A, Sabbagh M, Salloway S. Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimer’s Res Ther. 2021;13:98.

Article  Google Scholar 

Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimer’s Res Ther. 2021;13:80.

Article  Google Scholar 

Tampi RR, Forester BP, Agronin M. Aducanumab: evidence from clinical trial data and controversies. Drugs Context 2021;10:2021–2027.

Colom-Cadena M, Spires-Jones T, Zetterberg H, Blennow K, Caggiano A, DeKosky ST, et al. The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease. Alzheimer’s Res Ther. 2020;12:21.

Article  Google Scholar 

DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol. 1990;27:457–64.

Article  PubMed  Google Scholar 

Mecca AP, Chen M-K, O’Dell RS, Naganawa M, Toyonaga T, Godek TA, et al. In vivo measurement of widespread synaptic loss in Alzheimer’s disease with SV2A PET. Alzheimer’s Dement. 2020;16:974–82.

Article  Google Scholar 

Brier MR, Gordon B, Friedrichsen K, McCarthy J, Stern A, Christensen J, et al. Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med. 2016;8:338ra366.

Article  Google Scholar 

Sperling RA, Mormino EC, Schultz AP, Betensky RA, Papp KV, Amariglio RE, et al. The impact of amyloid-beta and tau on prospective cognitive decline in older individuals. Ann Neurol. 2019;85:181–93.

Article  PubMed  PubMed Central  Google Scholar 

Taddei RN, Perbet R, Mate de Gerando A, Wiedmer AE, Sanchez-Mico M, Connors Stewart T, et al. Tau oligomer–containing synapse elimination by microglia and astrocytes in Alzheimer disease. JAMA Neurol. 2023;80:1209–21.

Article  PubMed  PubMed Central  Google Scholar 

Arnsten AFT, Datta D, Del Tredici K, Braak H. Hypothesis: tau pathology is an initiating factor in sporadic Alzheimer’s disease. Alzheimers Dement. 2021;17:115–24.

Article  PubMed  Google Scholar 

Franzmeier N, Dehsarvi A, Steward A, Biel D, Dewenter A, Roemer SN, et al. Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer’s disease. Nat Commun. 2024;15:202.

Article  PubMed  PubMed Central  Google Scholar 

Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 2016;352:712–6.

Article  PubMed  PubMed Central  Google Scholar 

Bie B, Wu J, Foss JF, Naguib M. An overview of the cannabinoid type 2 receptor system and its therapeutic potential. Curr Opin Anaesthesiol. 2018;31:407–14.

Article  PubMed  PubMed Central  Google Scholar 

Dejanovic B, Huntley MA, De Mazière A, Meilandt WJ, Wu T, Srinivasan K, et al. Changes in the synaptic proteome in tauopathy and rescue of tau-induced synapse loss by C1q antibodies. Neuron. 2018;100:1322–36.e1327.

Article  PubMed  Google Scholar 

Shi Q, Chowdhury S, Ma R, Le KX, Hong S, Caldarone BJ, et al. Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice. Sci Transl Med. 2017;9:eaaf6295.

Article  PubMed  PubMed Central  Google Scholar 

Edwards DR, Handsley MM, Pennington CJ. The ADAM metalloproteinases. Mol Asp Med. 2008;29:258–89.

Article  Google Scholar 

Hsia H-E, Tüshaus J, Brummer T, Zheng Y, Scilabra SD, Lichtenthaler SF. Functions of ‘A disintegrin and metalloproteases (ADAMs)’ in the mammalian nervous system. Cell Mol Life Sci. 2019;76:3055–81.

Article  PubMed  PubMed Central  Google Scholar 

Whelan CD, Mattsson N, Nagle MW, Vijayaraghavan S, Hyde C, Janelidze S, et al. Multiplex proteomics identifies novel CSF and plasma biomarkers of early Alzheimer’s disease. Acta Neuropathol Commun. 2019;7:169.

Article  PubMed  PubMed Central  Google Scholar 

Llaurador-Coll M, Rios S, García-Gavilán JF, Babio N, Vilella E, Salas-Salvadó J. Plasma levels of neurology-related proteins are associated with cognitive performance in an older population with overweight/obesity and metabolic syndrome. Geroscience. 2023;45:2457–70.

Article  PubMed  PubMed Central  Google Scholar 

Brinkmalm A, Brinkmalm G, Honer WG, Frölich L, Hausner L, Minthon L, et al. SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer’s disease. Mol Neurodegener. 2014;9:53.

Article  PubMed  PubMed Central  Google Scholar 

Brinkmalm A, Dumurgier J, Brinkmalm G, Hansson O, Zetterberg H, Bouaziz-Amar E, et al. The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease. Alzheimer’s Res Ther. 2016;8:41.

Article  Google Scholar 

Wolfes AC, Dean C. The diversity of synaptotagmin isoforms. Curr Opin Neurobiol. 2020;63:198–209.

Article  PubMed  Google Scholar 

Antonucci F, Corradini I, Fossati G, Tomasoni R, Menna E, Matteoli M. SNAP-25, a known presynaptic protein with emerging postsynaptic functions. Front Synaptic Neurosci. 2016;8:7.

Article  PubMed  PubMed Central  Google Scholar 

Breitner J, Poirier J, Etienne P, Leoutsakos J. Rationale and structure for a new center for studies on prevention of Alzheimer’s disease (StoP-AD). J Prev Alzheimer’s Dis. 2016;3:236–42.

Google Scholar 

Picard C, Nilsson N, Labonté A, Auld D, Rosa-Neto P, Initiative tAsDN, et al. Apolipoprotein B is a novel marker for early tau pathology in Alzheimer’s disease. Alzheimer’s Dement. 2022;18:875–87.

Article  Google Scholar 

Lleó A, Alcolea D, Martínez-Lage P, Scheltens P, Parnetti L, Poirier J, et al. Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer’s disease continuum in the BIOMARKAPD study. Alzheimer’s Dement. 2019;15:742–53.

Article  Google Scholar 

McSweeney M, Pichet Binette A, Meyer PF, Gonneaud J, Bedetti C, Ozlen H, et al. Intermediate flortaucipir uptake is associated with Aβ-PET and CSF tau in asymptomatic adults. Neurology. 2020;94:e1190–200.

Article  PubMed  Google Scholar 

Ossenkoppele R, Rabinovici GD, Smith R, Cho H, Schöll M, Strandberg O, et al. Discriminative accuracy of [18F] flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2018;320:1151–62.

Article  PubMed  PubMed Central  Google Scholar 

Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998;20:310–9.

Article  PubMed  Google Scholar 

Jack CR Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14:535–62.

Article  PubMed  Google Scholar 

Tijms BM, Bertens D, Slot RE, Gouw AA, Teunissen CE, Scheltens P, et al. Low normal cerebrospinal fluid Aβ42 levels predict clinical progression in nondemented subjects. Ann Neurol. 2017;81:749–53.

Article  PubMed  Google Scholar 

Farrell ME, Kennedy KM, Rodrigue KM, Wig G, Bischof GN, Rieck JR, et al. Association of longitudinal cognitive decline with amyloid burden in middle-aged and older adults: evidence for a dose-response relationship. JAMA Neurol. 2017;74:830–8.

Article  PubMed  PubMed Central  Google Scholar 

Donohue MC, Sperling RA, Petersen R, Sun C-K, Weiner MW, Aisen PS, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317:2305–16.

Article  PubMed  PubMed Central  Google Scholar 

Meyer PF, Savard M, Poirier J, Labonté A, Rosa-Neto P, Weitz TM, et al. Bi-directional association of cerebrospinal fluid immune markers with stage of Alzheimer’s disease pathogenesis. J Alzheimers Dis. 2018;63:577–90.

Article