PSEN1 gene mutation
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Epidemiology
- two exceptional resilience mutation carriers carrying the Colombian PSEN1 p.Glu280Ala mutation have reportedly to escaped dementia for decades after the expected symptomatic age of Alzheimer onset
- whole-exome sequencing suggests a rare homozygous APOE variant (APOE3-Christchurch (p.Arg136Ser)) & a rare RELN variant (p.His3447Arg) conferred protection against dominantly inherited Alzheimer's disease
Function
- see presenilin-1
- putative catalytic subunit of APP-gamma-secretase
- presenilin-1 colocalizes with APP-gamma-secretase activity along with nicastrin, PEN-2 & APH1
- presenilins control proteolysis of APP, APLP-1 & Notch
- Notch-1 is thought to be the physiologic substrate of presenilin-1
More general terms
Additional terms
References
- ↑ Arboleda-Velasquez JF, Lopera F, O'Hare M et al Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019 Nov;25(11):1680-1683. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31686034 PMCID: PMC6898984 Free PMC article. https://pmc.ncbi.nlm.nih.gov/articles/PMC6898984/
- ↑ Lopera F, Marino C, Chandrahas AS et al Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBO heterozygous man. Nat Med. 2023 May;29(5):1243-1252. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37188781 PMCID: PMC10202812 Free PMC article. https://pmc.ncbi.nlm.nih.gov/articles/PMC10202812/
- ↑ Quiroz YT, Aguillon D, Aguirre-Acevedo DC et al APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease. N Engl J Med. 2024 Jun 20;390(23):2156-2164. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38899694 https://www.nejm.org/doi/10.1056/NEJMoa2308583