van der Flier WM, Scheltens P. The ATN framework—moving preclinical Alzheimer disease to clinical relevance. JAMA Neurol. 2022;79:968.

Article  PubMed  Google Scholar 

Tzioras M, McGeachan RI, Durrant CS, Spires-Jones TL. Synaptic degeneration in Alzheimer disease. Nat Rev Neurol. 2023;19:19–38.

Article  PubMed  Google Scholar 

Moscoso A, Grothe MJ, Ashton NJ, et al. Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum. Brain. 2021;144:325–39.

Article  PubMed  Google Scholar 

Janelidze S, Mattsson N, Palmqvist S, et al. Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat Med. 2020;26:379–86.

Article  CAS  PubMed  Google Scholar 

Teipel S, Drzezga A, Grothe MJ, et al. Multimodal imaging in Alzheimer’s disease: validity and usefulness for early detection. Lancet Neurol. 2015;14:1037–53.

Article  PubMed  Google Scholar 

Du YS, Chen X, Fu J, et al. RAGE and amyloid-β peptide neurotoxicity in Alzheimer’s disease. Nature. 1996;382:685–91.

Article  Google Scholar 

Lee A, Kondapalli C, Virga DM, et al. Aβ42 oligomers trigger synaptic loss through CAMKK2-AMPK-dependent effectors coordinating mitochondrial fission and mitophagy. Nat Commun. 2022;13:4444.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rother C, Uhlmann RE, Müller SA, et al. Experimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae. Nat Commun. 2022;13:7333.

Article  PubMed  PubMed Central  Google Scholar 

Milà-Alomà M, Salvadó G, Gispert JD, et al. Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer’s continuum. Alzheimer’s Dement. 2020;16:1358–71. https://doi.org/10.1002/alz.12131.

Article  Google Scholar 

Dawe RJ, Yu L, Arfanakis K, Schneider JA, Bennett DA, Boyle PA. Late-life cognitive decline is associated with hippocampal volume, above and beyond its associations with traditional neuropathologic indices. Alzheimer’s Dement. 2020;16:209–18. https://doi.org/10.1002/alz.12009.

Article  Google Scholar 

Duits FH, Brinkmalm G, Teunissen CE, et al. Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer’s disease. Alzheimers Res Ther. 2018;10:5. https://doi.org/10.1186/s13195-017-0335-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang H, Therriault J, Kang MS, et al. Cerebrospinal fluid synaptosomal-associated protein 25 is a key player in synaptic degeneration in mild cognitive impairment and Alzheimer’s disease. Alzheimers Res Ther. 2018;10:80. https://doi.org/10.1186/s13195-018-0407-6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nilsson J, Ashton NJ, Benedet AL, et al. Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer’s disease. Alzheimers Res Ther. 2022;14:78. https://doi.org/10.1186/s13195-022-01021-8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu Y. Early increase of cerebrospinal fluid 14-3–3ζ protein in the Alzheimer’s disease continuum. Front Aging Neurosci. 2022. https://doi.org/10.3389/fnagi.2022.941927/full.

Article  PubMed  PubMed Central  Google Scholar 

Pascoal TA, Benedet AL, Ashton NJ, et al. Publisher correction: microglial activation and tau propagate jointly across Braak stages. Nat Med. 2021;27:2048–9.

Article  CAS  PubMed  Google Scholar 

Contreras JA, Aslanyan V, Albrecht DS, Mack WJ, Pa J. Higher baseline levels of CSF inflammation increase risk of incident mild cognitive impairment and Alzheimer’s disease dementia. Alzheimer’s Dement Diagnosis Assess Dis Monit. 2022. https://doi.org/10.1002/dad2.12346.

Article  Google Scholar 

Hong S, Beja-Glasser VF, Nfonoyim BM, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 2016;352:712–6. https://doi.org/10.1126/science.aad8373.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Colonna M. The biology of TREM receptors. Nat Rev Immunol. 2023.

Morenas-Rodríguez E, Li Y, Nuscher B, et al. Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer’s disease: a longitudinal observational study. Lancet Neurol. 2022;21:329–41.

Article  PubMed  PubMed Central  Google Scholar 

Zhao A, Jiao Y, Ye G, et al. Soluble TREM2 levels associate with conversion from mild cognitive impairment to Alzheimer’s disease. J Clin Invest. 2022;132.

Winfree RL, Seto M, Dumitrescu L, et al. TREM2 gene expression associations with Alzheimer’s disease neuropathology are region-specific: implications for cortical versus subcortical microglia. Acta Neuropathol. 2023. https://doi.org/10.1007/s00401-023-02564-2.

Article  PubMed  PubMed Central  Google Scholar 

Therriault J, Benedet AL, Pascoal TA, et al. Determining amyloid-β positivity using 18 F-AZD4694 PET imaging. J Nucl Med. 2021;62:247–52. https://doi.org/10.2967/jnumed.120.245209.

Article  CAS  PubMed  Google Scholar 

Pascoal TA, Therriault J, Benedet AL, et al. 18F-MK-6240 PET for early and late detection of neurofibrillary tangles. Brain. 2020;143:2818–30.

Article  PubMed  Google Scholar 

Pascoal TA, Shin M, Kang MS, et al. In vivo quantification of neurofibrillary tangles with [18F]MK-6240. Alzheimers Res Ther. 2018;10:74. https://doi.org/10.1186/s13195-018-0402-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. Neuroimage. 2009;46:39–46.

Article  PubMed  Google Scholar 

Tward DJ, Sicat CS, Brown T, et al. Entorhinal and transentorhinal atrophy in mild cognitive impairment using longitudinal diffeomorphometry. Alzheimer’s Dement Diagnosis, Assess Dis Monit. 2017;9:41–50. https://doi.org/10.1016/j.dadm.2017.07.005.

Article  Google Scholar 

Tovey SC, Dedos SG, Taylor EJA, Church JE, Taylor CW. Selective coupling of type 6 adenylyl cyclase with type 2 IP3 receptors mediates direct sensitization of IP3 receptors by cAMP. J Cell Biol. 2008;183:297–311.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59. https://doi.org/10.1007/BF00308809.

Article  CAS  PubMed  Google Scholar 

Braak H, Braak E. Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging. 1995;16:271–8.

Article  CAS  PubMed  Google Scholar 

Therriault J, Pascoal TA, Lussier FZ, et al. Biomarker modeling of Alzheimer’s disease using PET-based Braak staging. Nat Aging. 2022;2:526–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nilsson J, Gobom J, Sjödin S, et al. Cerebrospinal fluid biomarker panel for synaptic dysfunction in Alzheimer’s disease. Alzheimer’s Dement Diagnosis Assess Dis Monit. 2021. https://doi.org/10.1002/dad2.12179.

Article  Google Scholar 

Rosseel Y. lavaan: An R package for structural equation modeling. J Stat Softw. 2012;48.

Jayaratnam S, Khoo AKL, Basic D. Rapidly progressive Alzheimer’s disease and elevated 14-3–3 proteins in cerebrospinal fluid. Age Ageing. 2008;37:467–9. https://doi.org/10.1093/ageing/afn094.

Article  PubMed  Google Scholar 

Ashton NJ, Janelidze S, Al Khleifat A, et al. A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021;12:3400.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Visser PJ, Reus LM, Gobom J, et al. Correction: cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease. Mol Neurodegener. 2022;17:37. https://doi.org/10.1186/s13024-022-00540-0.

Article  PubMed  PubMed Central  Google Scholar 

Henneman WJP, Sluimer JD, Barnes J, et al. Hippocampal atrophy rates in Alzheimer disease: added value over whole brain volume measures. Neurology. 2009;72:999–1007. https://doi.org/10.1212/01.wnl.0000344568.09360.31.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu W, Lin H, He X, et al. Neurogranin as a cognitive biomarker in cerebrospinal fluid and blood exosomes for Alzheimer’s disease and mild cognitive impairment. Transl Psychiatry. 2020;10:125.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhong L, Chen X-F, Wang T, et al. Soluble TREM2 induces inflammatory responses and enhances microglial survival. J Exp Med. 2017;214:597–607.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rueda-Carrasco J, Sokolova D, Lee S, et al. Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer’s disease models. EMBO J. 2023.