Tanzi RE. The genetics of alzheimer disease. Cold Spring Harb Perspect Med. 2012;2:a0062c96.

Article  Google Scholar 

Pavisic IM, Nicholas JM, O’Connor A, Rice H, Lu K, Fox NC, et al. Disease duration in autosomal dominant familial Alzheimer disease. Neurol Genet. 2020;6:e507.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Karch CM, Cruchaga C, Goate AM. Alzheimer’s disease genetics: from the bench to the clinic. Neuron. 2014;83:11–26.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, et al. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014;83:253–60.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Cai Y, An SSA, Kim S. Mutations in presenilin 2 and its implications in Alzheimer’s disease and other dementia-associated disorders. Clin Interv Aging. 2015;10:1163–72.

PubMed  PubMed Central  Google Scholar 

Dai M-H, Zheng H, Zeng L-D, Zhang Y. The genes associated with early-onset Alzheimer’s disease. Oncotarget. 2017;9:15132–43.

Article  PubMed  PubMed Central  Google Scholar 

De Strooper B, Iwatsubo T, Wolfe MS. Presenilins and γ-secretase: structure, function, and role in alzheimer disease. Cold Spring Harb Perspect Med. 2012;2:a006304.

Article  PubMed  PubMed Central  Google Scholar 

Hsu S, Pimenova AA, Hayes K, Villa JA, Rosene MJ, Jere M, et al. Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiol Dis. 2020;139:104817.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Petit D, Fernández SG, Zoltowska KM, Enzlein T, Ryan NS, O’Connor A, et al. Aβ profiles generated by Alzheimer’s disease causing PSEN1 variants determine the pathogenicity of the mutation and predict age at disease onset. Mol Psychiatry. 2022;27:2821–32.

Kwart D, Gregg A, Scheckel C, Murphy EA, Paquet D, Duffield M, et al. A Large Panel of Isogenic APP and PSEN1 Mutant Human iPSC Neurons Reveals Shared Endosomal Abnormalities Mediated by APP β-CTFs. Not Aβ Neuron. 2019;104:256–270.e5.

Article  PubMed  CAS  Google Scholar 

Haapasalo A, Kovacs DM. The many substrates of presenilin/γ-secretase. J Alzheimers Dis. 2011;25:3–28.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bagaria J, Bagyinszky E, An SSA. Genetics, functions, and clinical impact of Presenilin-1 (PSEN1) gene. Int J Mol Sci. 2022;23:10970.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Güner G, Lichtenthaler SF. The substrate repertoire of γ-secretase/presenilin. Semin Cell Dev Biol. 2020;105:27–42.

Article  PubMed  Google Scholar 

Battaglia M, Ahmed S, Anderson MS, Atkinson MA, Becker D, Bingley PJ, et al. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes Care. 2020;43:5–12.

Article  PubMed  Google Scholar 

Caldwell AB, Liu Q, Schroth GP, Galasko DR, Yuan SH, Wagner SL, et al. Dedifferentiation and neuronal repression define familial Alzheimer’s disease. Sci Adv. 2020;6:eaba5933.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mertens J, Herdy JR, Traxler L, Schafer ST, Schlachetzki JCM, Böhnke L, et al. Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients. Cell Stem Cell. 2021;28:1533–1548.e6.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Frost B. Alzheimer’s disease and related tauopathies: disorders of disrupted neuronal identity. Trends Neurosci. 2023;S0166–2236(23):00166–72.

Google Scholar 

Caldwell AB, Anantharaman BG, Ramachandran S, Nguyen P, Liu Q, Trinh I, et al. Transcriptomic profiling of sporadic Alzheimer’s disease patients. Mol Brain. 2022;15:83.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Patel AO, Caldwell AB, Ramachandran S, Subramaniam S. Endotype Characterization Reveals Mechanistic Differences Across Brain Regions in Sporadic Alzheimer’s Disease. J Alzheimers Dis Rep. 2023;7(1):957-72.

Article  PubMed Central  Google Scholar 

Andrade-Guerrero J, Santiago-Balmaseda A, Jeronimo-Aguilar P, Vargas-Rodríguez I, Cadena-Suárez AR, Sánchez-Garibay C, et al. Alzheimer’s disease: an updated overview of its genetics. Int J Mol Sci. 2023;24:3754.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Jayadev S, Leverenz JB, Steinbart E, Stahl J, Klunk W, Yu C-E, et al. Alzheimer’s disease phenotypes and genotypes associated with mutations in presenilin 2. Brain. 2010;133:1143–54.

Article  PubMed  PubMed Central  Google Scholar 

Zhang G, Xie Y, Wang W, Feng X, Jia J. Clinical characterization of an APP mutation (V717I) in five Han Chinese families with early-onset Alzheimer’s disease. J Neurol Sci. 2017;372:379–86.

Article  PubMed  CAS  Google Scholar 

Goate A, Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature. 1991;349:704–6.

Article  PubMed  CAS  Google Scholar 

Cruts M, van Duijn CM, Backhovens H, Van den Broeck M, Wehnert A, Serneels S, et al. Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile alzheimer disease. Hum Mol Genet. 1998;7:43–51.

Article  PubMed  CAS  Google Scholar 

Liu Q, Waltz S, Woodruff G, Ouyang J, Israel MA, Herrera C, et al. Effect of potent γ-secretase modulator in human neurons derived from multiple presenilin 1–induced pluripotent stem cell mutant carriers. JAMA Neurol. 2014;71:1481–9.

Article  PubMed  PubMed Central  Google Scholar 

Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C, et al. Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature. 2012;482:216–20.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Karch CM, Hernández D, Wang J-C, Marsh J, Hewitt AW, Hsu S, et al. Human fibroblast and stem cell resource from the dominantly inherited alzheimer network. Alzheimer’s Res Ther. 2018;10:69.

Article  Google Scholar 

Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, et al. A more efficient method to generate integration-free human iPS cells. Nat Methods. 2011;8:409–12.

Article  PubMed  CAS  Google Scholar 

Yuan SH, Hiramatsu N, Liu Q, Sun XV, Lenh D, Chan P, et al. Tauopathy-associated PERK alleles are functional hypomorphs that increase neuronal vulnerability to ER stress. Hum Mol Genet. 2018;27:3951–63.

PubMed  PubMed Central  CAS  Google Scholar 

Yuan SH, Martin J, Elia J, Flippin J, Paramban RI, Hefferan MP, et al. Cell-surface marker signatures for the isolation of neural stem cells, glia and neurons derived from human pluripotent stem cells. PLoS One. 2011;6:e17540.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Woodruff G, Young JE, Martinez FJ, Buen F, Gore A, Kinaga J, et al. The Presenilin-1 ΔE9 mutation results in reduced γ-secretase activity, but not total loss of ps1 function, in isogenic human stem cells. Cell Rep. 2013;5:974–85.

Article  PubMed  CAS  Google Scholar 

Knupp A, Mishra S, Martinez R, Braggin JE, Szabo M, Kinoshita C, et al. Depletion of the AD risk gene SORL1 selectively impairs neuronal endosomal traffic independent of amyloidogenic APP processing. Cell Rep. 2020;31:107719.