Your APOE status is the single most important common genetic risk factor for late-onset Alzheimer's disease.
The apolipoprotein E gene governs how your brain clears beta-amyloid and how your liver processes lipoproteins. The same gene, two critical systems.
The Biology
The apolipoprotein E gene produces a protein that plays a central role in how your brain clears beta-amyloid. The protein fragment that accumulates into the plaques characteristic of Alzheimer's disease. APOE also governs how your liver processes cholesterol and lipoproteins. The same gene that affects your cardiovascular lipid metabolism is also a master regulator of your brain's waste-clearance system.
What Varia Analyzes
APOE status comes from reading rs429358 (codon 112) and rs7412 (codon 158) together; neither position alone is enough. Your alleles at both positions determine which APOE isoforms you carry: ε2, ε3, or ε4. Varia reads both positions from your raw file and resolves your APOE diplotype. 23andMe's FDA-authorized Genetic Health Risk reports cover a late-onset Alzheimer's report based on APOE e4 status; Varia is not FDA-authorized and performs no detection. AncestryDNA chip files do not reliably report the APOE marker rs429358, so Varia's scanner does not treat that marker as determinable from those files.
Why It Matters
About 25 percent of people of European descent carry ε3/ε4, which published studies associate with roughly 3 to 4 times the Alzheimer's risk of the common ε3/ε3 genotype. About 2 to 3 percent carry ε4/ε4, associated with roughly 8 to 14 times that risk. These are population associations, not a prediction: many ε4/ε4 carriers never develop Alzheimer's disease. APOE is the strongest common genetic signal for late-onset Alzheimer's, and a result here is something to talk through with a clinician or genetic counselor.
Polygenic Risk Scores
Varia's catalog resolves APOE diplotype from rs429358 and rs7412, the dominant common-variant signal in late-onset Alzheimer's disease. Polygenic risk scores (PRS) combine many additional common variants into a population-level LOAD estimate. Published work shows a PRS adds modest predictive information beyond APOE genotype, including within ε4 carriers, but no guideline endorses routine clinical AD-PRS use. Varia publishes an editorial entry on what those scores are and where validated assessment comes from. Varia does not compute a per-user AD-PRS from a consumer file. See Polygenic Risk Scores.
Key Sources
- Corder EH, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease. Science. 1993.
- Farrer LA, et al. Effects of age, sex, and ethnicity on the association between APOE genotype and Alzheimer disease. JAMA. 1997.
- Liu CC, et al. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013.
- Yamazaki Y, et al. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol. 2019.