# APOE genotype (ε2/ε3/ε4)

Apolipoprotein E (APOE) is a fat-transport protein, coded by the APOE gene. The gene comes in three versions (alleles): ε2, ε3, and ε4, giving six possible genotypes. The ε4 allele is the strongest common genetic risk factor for late-onset Alzheimer's. One copy roughly triples your risk; two copies (ε4/ε4) raise it about 10 to 15 times (Farrer 1997 meta-analysis). A 2024 study (Fortea et al., Nature Medicine) even proposed treating ε4/ε4 as a near-deterministic genetic form of late-onset Alzheimer's, though that is still debated. The ε2 allele goes the other way: it is modestly protective against Alzheimer's and linked to lower LDL. Because your APOE genotype is fixed at birth and has large, well-replicated effects, it is uniquely useful for gauging your lifetime dementia and heart risk. But penetrance is incomplete, and lifestyle can shift the trajectory.

## Sources

- Fortea J, Pegueroles J, Alcolea D, et al.. (2024). APOE4 homozygosity represents a distinct genetic form of Alzheimer's disease. Nature Medicine. https://doi.org/10.1038/s41591-024-02931-w

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_Canonical: https://longevity-switzerland.com/en/glossary/apoe-genotype · Part of Longevity Cities · Updated 2026-06-22_