Apolipoprotein Eε4 modifies Alzheimer's disease onset in an E280A PS1 kindred
Abstract
We previously have identified a large kindred from Colombia in which Alzheimer's disease (AD) is caused by the E280A presenilin 1 (PS1) mutation. The objective of this study was to examine whether environmental and genetic factors are responsible for variation in the phenotypic expression of the E280A PS1 mutation. We genotyped coding and promoter polymorphisms of the APOE gene in carriers of the E280A PS1 mutation. Kaplan–Meier product‐limit and Cox proportional hazard models were used in the statistical analyses. DNA was available from 114 carriers of the E280A PS1 mutation, including 52 subjects with AD. APOE ε 4 allele carriers were more likely to develop AD at an earlier age than subjects without the ε 4 allele (hazard ratio, 2.07; 95% confidence interval, 1.07–3.99; p = 0.030). Subjects with low education were more likely to develop AD later than those with higher education (hazard ratio, 0.476; 95% confidence interval, 0.26–0.87). Low educational level was associated with rural residence (p < 0.001). Promoter APOE variants did not influence either the onset or the duration of the disease. This study is the first to our knowledge to demonstrate that genetic and environmental factors influence age of onset in a kindred with a familial AD mutation. Ann Neurol 2003
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The second study found that the APOE*E2 allele had a modest statistically nonsignificant ADAOO decelerator effect.
“and that the APOE*E2 allele had a modest statistically nonsignificant ADAOO decelerator effect.42”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [42]
The second study expanded the number of patients with the E280A mutation to 52 and found that carriers of the APOE ɛ4 allele were more likely to develop AD at an earlier age than non-carriers (hazard ratio=2.07; 95% CI=1.07-3.99; P<0.03).
“The second study expanded the number of patients with the E280A mutation to 52 and found that carriers of the APOE ɛ4 allele were more likely to develop AD at an earlier age than non-carriers (hazard ratio=2.07; 95% CI=1.07–3.99; P<0.03)”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [42]
The APOE ε4 allele reduces age at onset in both familial and sporadic Alzheimer's disease.
“The best known genetic modulator of AD AAO, the APOE ɛ4 allele, reduces AAO in both familial and sporadic AD,6, 7”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [7]
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- Authors
- Pastor, P., Roe, C. M., Villegas, A., Bedoya, G., Chakraverty, S., García, G., Tirado, V., Norton, J., Ríos, S., Martínez, M., Kosik, K. S., Lopera, F., & Goate, A. M.
- Affiliations
- Washington University in St. Louis (US)
- Universidad de Antioquia (CO)
- Brigham and Women's Hospital (US)
- Corresponding author
- Goate, Alison M.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2003-07-25
- Volume
- 54
- Issue
- 2
- Pages
- 163-169
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2056614031
- Cited by
- 194
- References
- 42
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 12 · 2021: 11 · 2020: 12 · 2019: 10 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 10 · 2014: 9 · 2013: 6 · 2012: 8
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- COLCIENCIAS (115-04-007-99; F.L.)
- NIA (P50 AG05681 A.M.G C.M.R., P01 AG03991)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, presenilin 1, APOE ε4, age of onset, familial Alzheimer's disease, APOE promoter polymorphisms, educational attainment, rural residence, genetic and environmental risk factors
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Colombia, DNA, Education, Environment, Female, Heterozygote, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Pedigree, Phenotype, Polymorphism, Genetic, Promoter Regions, Genetic, Rural Population, Survival Analysis, Age of Onset, Apolipoprotein E4, Presenilin-1
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