ArticlePloS one2019
The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- The impact of PPARγ and ApoE gene polymorphisms on susceptibility to diabetic kidney disease in type 2 diabetes mellitus: a meta-analysis.BMC nephrology · 2024Pooled it
- Cognitive Functioning of Unaffected First-degree Relatives of Individuals With Late-onset Alzheimer's Disease: A Systematic Literature Review and Meta-analysis.Neuropsychology review · 2023Pooled it
- Pooled it
- Effect of APOE Genotype on Plasma Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid, Arachidonic Acid, and Hippocampal Volume in the Alzheimer's Disease Cooperative Study-Sponsored DHA Clinical Trial.Journal of Alzheimer's disease : JAD · 2020Trial
- The Association BetweenNeurology. Genetics · 2026Article
- Article
- Plasma proteomics ofmedRxiv : the preprint server for health sciences · 2026Article
- ModelingFrontiers in genetics · 2026Article
- Facial Appearance and Markers of Cardiometabolic Risk in Healthy Adult Men.Archives of sexual behavior · 2025Article
- The economic burden of subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia: excess costs and associated clinical and risk factors.Alzheimer's research & therapy · 2025Article
- Whole-genome sequencing reveals the impact of lipid pathway and APOE genotype on brain amyloidosis.Human molecular genetics · 2025Article
- AAVrh.10 delivery of novel APOE2-Christchurch variant suppresses amyloid and Tau pathology in Alzheimer's disease mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- APOE epsilon variants and composite risk of dementia, disability, and death in the health and retirement study.Journal of the American Geriatrics Society · 2024Article
- Multifaceted roles of APOE in Alzheimer disease.Nature reviews. Neurology · 2024Review
- Association of LIfestyle for BRAin health risk score (LIBRA) and genetic susceptibility with incident dementia and cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Association of Apolipoprotein E (APOE) Polymorphisms With Serological Lipid and Inflammatory Markers.Cureus · 2024Article
- Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3.Aging and disease · 2024Article
- Association between metabolic syndrome and risk of incident dementia in UK Biobank.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics.International journal of medical sciences · 2024Review
- How are APOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis.Frontiers in aging · 2024Article
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Authors and funding
19 authors at 9 institutions in 3 countries.
Funding
Abstract
backgroundApolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-ε2 allele on diseases in the elderly and survival remains elusive.
methodsWe aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-ε2, with survival in the population.
resultsDuring a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1*10-2), whereas APOE-ε4 carriers were at increased risk of death (HR 1.17,1.12-1.21; P = 2.8*10-16). APOE was associated with mortality risk in a dose-dependent manner, with risk estimates lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). After censoring for dementia, effect estimates remained similar for APOE-ε2 (HR 0.95,0.90-1.01), but attenuated for APOE-ε4 (HR 1.07,1.01-1.12). Results were broadly similar across cohorts, and did not differ by age or sex. APOE genotype was associated with baseline lipid fractions (e.g. mean difference(95%CI) in LDL(mg/dL) for ε2 versus ε33: -17.1(-18.1-16.0), and ε4 versus ε33: +5.7(4.8;6.5)), but the association between APOE and mortality was unaltered after adjustment for baseline LDL or cardiovascular disease. Given the European ancestry of the study population, results may not apply to other ethnicities.
conclusionCompared with APOE-ε3, APOE-ε2 is associated with prolonged survival, whereas mortality risk is increased for APOE-ε4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-ε2 in health and disease.
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