Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, Cummings J, van der Flier WM. Alzheimer’s disease. Lancet. 2021;397:1577–90.
Article PubMed PubMed Central CAS Google Scholar
Chavez-Gutierrez L, Szaruga M. Mechanisms of neurodegeneration - Insights from familial Alzheimer’s disease. Semin Cell Dev Biol. 2020;105:75–85.
Article PubMed CAS Google Scholar
Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, Goate A, Frommelt P, Ghetti B, Langbaum JB, 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
Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, Salloway S, Sperling RA, Windisch M, Xiong C. Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease. Alzheimers Res Ther. 2011;3:1.
Article PubMed PubMed Central Google Scholar
Acx H, Chavez-Gutierrez L, Serneels L, Lismont S, Benurwar M, Elad N, De Strooper B. Signature amyloid beta profiles are produced by different gamma-secretase complexes. J Biol Chem. 2014;289:4346–55.
Article PubMed CAS Google Scholar
Sannerud R, Esselens C, Ejsmont P, Mattera R, Rochin L, Tharkeshwar AK, De Baets G, De Wever V, Habets R, Baert V, et al. Restricted Location of PSEN2/gamma-Secretase Determines Substrate Specificity and Generates an Intracellular Abeta Pool. Cell. 2016;166:193–208.
Article PubMed PubMed Central CAS Google Scholar
Takami M, Nagashima Y, Sano Y, Ishihara S, Morishima-Kawashima M, Funamoto S, Ihara Y. gamma-Secretase: successive tripeptide and tetrapeptide release from the transmembrane domain of beta-carboxyl terminal fragment. J Neurosci. 2009;29:13042–52.
Article PubMed PubMed Central CAS Google Scholar
Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, et al. Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999;286:735–41.
Article PubMed CAS Google Scholar
Chavez-Gutierrez L, Bammens L, Benilova I, Vandersteen A, Benurwar M, Borgers M, Lismont S, Zhou L, Van Cleynenbreugel S, Esselmann H, et al. The mechanism of gamma-Secretase dysfunction in familial Alzheimer disease. EMBO J. 2012;31:2261–74.
Article PubMed PubMed Central CAS Google Scholar
Szaruga M, Veugelen S, Benurwar M, Lismont S, Sepulveda-Falla D, Lleo A, Ryan NS, Lashley T, Fox NC, Murayama S, et al. Qualitative changes in human gamma-secretase underlie familial Alzheimer’s disease. J Exp Med. 2015;212:2003–13.
Article PubMed PubMed Central CAS Google Scholar
Szaruga M, Munteanu B, Lismont S, Veugelen S, Horre K, Mercken M, Saido TC, Ryan NS, De Vos T, Savvides SN, et al. Alzheimer’s-Causing Mutations Shift Abeta Length by Destabilizing gamma-Secretase-Abetan Interactions. Cell. 2017;170(443–456): e414.
Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, Hutton M, Buee L, Harigaya Y, Yager D, et al. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature. 1996;383:710–3.
Article PubMed CAS Google Scholar
Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, Prada CM, Kim G, Seekins S, Yager D, et al. Familial Alzheimer’s disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron. 1996;17:1005–13.
Article PubMed CAS Google Scholar
Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, et al. 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. 1996;2:864–70.
Article PubMed CAS Google Scholar
Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, et al. Mutant presenilins of Alzheimer’s disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat Med. 1997;3:67–72.
Article PubMed CAS Google Scholar
Murayama O, Tomita T, Nihonmatsu N, Murayama M, Sun X, Honda T, Iwatsubo T, Takashima A. Enhancement of amyloid beta 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer’s disease. Neurosci Lett. 1999;265:61–3.
Article PubMed CAS Google Scholar
Veugelen S, Saito T, Saido TC, Chavez-Gutierrez L, De Strooper B. Familial Alzheimer’s Disease Mutations in Presenilin Generate Amyloidogenic Abeta Peptide Seeds. Neuron. 2016;90:410–6.
Article PubMed CAS Google Scholar
Saito T, Suemoto T, Brouwers N, Sleegers K, Funamoto S, Mihira N, Matsuba Y, Yamada K, Nilsson P, Takano J, et al. Potent amyloidogenicity and pathogenicity of Abeta43. Nat Neurosci. 2011;14:1023–32.
Article PubMed CAS Google Scholar
Kretner B, Trambauer J, Fukumori A, Mielke J, Kuhn PH, Kremmer E, Giese A, Lichtenthaler SF, Haass C, Arzberger T, Steiner H. Generation and deposition of Abeta43 by the virtually inactive presenilin-1 L435F mutant contradicts the presenilin loss-of-function hypothesis of Alzheimer’s disease. EMBO Mol Med. 2016;8:458–65.
Article PubMed PubMed Central CAS Google Scholar
Seuma M, Lehner B, Bolognesi B. An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation. Nat Commun. 2022;13:7084.
Article PubMed PubMed Central CAS Google Scholar
Zhang Y, Chen H, Li R, Sterling K, Song W. Amyloid beta-based therapy for Alzheimer’s disease: challenges, successes and future. Signal Transduct Target Ther. 2023;8:248.
Article PubMed PubMed Central CAS Google Scholar
Jucker M, Walker LC. Alzheimer’s disease: From immunotherapy to immunoprevention. Cell. 2023;186:4260–70.
Article PubMed PubMed Central CAS Google Scholar
Petit D, Fernandez SG, Zoltowska KM, Enzlein T, Ryan NS, O’Connor A, Szaruga M, Hill E, Vandenberghe R, Fox NC, Chavez-Gutierrez L. Abeta 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.
Article PubMed PubMed Central CAS Google Scholar
Schultz SA, Liu L, Schultz AP, Fitzpatrick CD, Levin R, Bellier JP, Shirzadi Z, Joseph-Mathurin N, Chen CD, Benzinger TLS, et al. gamma-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer’s disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). Lancet Neurol. 2024;23:913–24.
Article PubMed CAS Google Scholar
Ryan NS, Nicholas JM, Weston PSJ, Liang Y, Lashley T, Guerreiro R, Adamson G, Kenny J, Beck J, Chavez-Gutierrez L, et al. Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer’s disease: a case series. Lancet Neurol. 2016;15:1326–35.
Wang G, Zhang DF, Jiang HY, Fan Y, Ma L, Shen Z, Bi R, Xu M, Tan L, Shan B, et al. Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer’s disease. J Psychiatr Res. 2019;113:141–7.
Jia L, Fu Y, Shen L, Zhang H, Zhu M, Qiu Q, Wang Q, Yan X, Kong C, Hao J, et al. PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer’s disease. Alzheimers Dement. 2020;16:178–91.
Mao C, Li J, Dong L, Huang X, Lei D, Wang J, Chu S, Liu C, Peng B, Roman GC, et al. Clinical Phenotype and Mutation Spectrum of Alzheimer’s Disease with Causative Genetic Mutation in a Chinese Cohort. Curr Alzheimer Res. 2021;18:265–72.
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