May 18, 2026 · 6 min read

APOE and rs429358: the Alzheimer's gene explained

If you've ever read about consumer DNA testing, you've probably seen the variant rs429358 mentioned. It sits in the APOE gene on chromosome 19 and, together with a second variant rs7412, defines the famous APOE ε2/ε3/ε4 alleles. One of those — ε4 — is the strongest common genetic risk factor for late-onset Alzheimer's disease known to science.

What rs429358 is, in one paragraph

APOE codes for apolipoprotein E, a protein that carries cholesterol in the brain. At position rs429358, you carry either a T or a C. A T at that position contributes to the ε2 or ε3 allele; a C contributes to ε4. Since you have two copies of chromosome 19, your genotype is two letters — TT, CT or CC — and the combination with rs7412 determines whether you carry zero, one or two copies of the ε4 allele.

The numbers that matter

Compared to people with two ε3 copies (the most common combination), carriers of a single ε4 allele have roughly 3× higher lifetime risk of Alzheimer's. Carriers of two ε4 copies — about 2% of the population — have approximately 8–12× higher risk, with earlier average age of onset. These numbers come from large meta-analyses; the GWAS Catalog lists hundreds of replications.

What it doesn't tell you

A high-risk APOE genotype is not a diagnosis or a prediction. The majority of ε4 carriers never develop Alzheimer's, and many non-carriers do. Risk is also modulated by other genes (TREM2, CLU, PICALM, dozens more), age, cardiovascular health, education, sleep and lifestyle. APOE explains a meaningful slice of the variation between people, not the outcome for any one person.

And the ancestry footnote matters: most of the foundational APOE studies were done in European-ancestry populations. The risk multipliers are smaller in African and East Asian populations, in part because of different background allele frequencies and in part because of gene-environment interactions we don't fully understand yet.

How to check yours

If you already have a raw DNA file from 23andMe or AncestryDNA, both variants (rs429358 and rs7412) are reliably included on every recent chip. Upload your file and our report will combine them into the ε2/ε3/ε4 interpretation, explain the odds ratios in everyday language, and link to the peer-reviewed studies behind the numbers.

If you'd rather not know your APOE status, that's a legitimate choice — many clinicians actively discourage testing without genetic counseling because the psychological impact of an ε4/ε4 result is real. Our report shows the result only inside a collapsible card that you can choose not to open.

Further reading

• Polygenic risk scores (PRS) for non-scientists → — APOE is a strong single variant, but most disease risk is polygenic.
• Our methodology → — how we compute risk scores from GWAS data.

This article is for educational purposes only and does not constitute medical advice. If you have concerns about Alzheimer's risk, please consult a healthcare professional or genetic counselor.