The APOE genotypes explained: from 2/2 to 4/4

Your APOE genotype is a pair, one allele from each parent, and it is one of the most-studied genetic influences on both Alzheimer’s and cardiovascular risk. The pairs range from 2/2, which carries an exceptionally low Alzheimer’s risk, to 4/4, which carries the highest. This page shows you how to read your own result with the actual numbers, not just “higher” and “lower.”

The three alleles

The gene comes in three common versions: ε2, ε3, and ε4 (often written 2, 3, 4).

• ε2 is the least common, roughly 5 to 10% of copies in most populations, and is tied to lower Alzheimer’s risk. It is the protective one, with its own quirk: it can raise triglycerides and, rarely, contributes to a lipid disorder.
• ε3 is the most common worldwide, the majority of copies, and is the neutral reference everything else is measured against.
• ε4 is roughly 14% of copies (it varies widely by ancestry) and is tied to higher risk of late-onset Alzheimer’s and, to a degree, cardiovascular disease.

Because you carry two copies, those alleles combine into six possible genotypes.

The six genotypes, with the risk picture

The pattern that runs through the whole table is dose-dependent: risk rises with each ε4 copy, and falls with each ε2. That comes from the classic 1997 meta-analysis by Farrer and colleagues. The figures below are measured relative to 3/3 and mostly in people of European ancestry. To make them mean something, anchor to the baseline: a 3/3 person has roughly a 10 to 15% lifetime risk of Alzheimer’s dementia by age 85. The absolute ranges are wide on purpose, because they move with age, sex, and ancestry.

Genotype	How common	Relative risk vs 3/3	Approx. lifetime risk by 85
2/2	rare (~0.5%)	~0.1x (about 90% lower)	very low
2/3	~10 to 15%	below average	below ~10%
2/4	~2%	intermediate	modestly above 3/3
3/3	most common (~55 to 60%)	reference (1x)	~10 to 15%
3/4	~20 to 25%	~3 to 4x	~20 to 30%
4/4	~2 to 3%	~9 to 15x	~30 to 60%

Three rows deserve their full weight.

The 2/2 protection is striking. In a 5,000-person autopsy study, two ε2 copies carried an odds ratio of 0.13 versus 3/3, roughly a 90% lower likelihood of Alzheimer’s.

At the other end, 4/4 keeps looking more consequential the closer researchers look. A 2024 study found more than 95% of 4/4 carriers already show Alzheimer’s biomarkers by age 55, with most developing symptoms by their mid-60s, and argued that 4/4 is penetrant enough to count as a distinct genetic form of the disease rather than just a risk factor.

The 2/4 genotype is the genuinely ambiguous one. The protective ε2 only partly offsets the ε4, and in several analyses the risk lands closer to 3/4 than the reassuring phrase “a little above average” suggests.

Two-copy results of either kind are uncommon. Roughly a quarter of people carry one ε4 copy, and only about 2 to 3% carry two, so a 4/4 result is genuinely rare, which is part of why it can feel isolating. For a calm orientation, see Start Here.

How much earlier does onset come?

This is the part that makes one copy feel different from two, and it is not captured by lifetime risk alone. Among carriers who do develop Alzheimer’s, the average age of symptom onset drops with each ε4 copy: roughly the mid-80s for 3/3, a few years earlier for 3/4, and often into the late 60s for 4/4, a shift of more than a decade. That earlier onset is why 4/4 changes the planning horizon, and why prevention conversations tend to start younger for two-copy carriers.

Three caveats that change how you read the numbers

• Risk is not destiny. Many 4/4 carriers never develop Alzheimer’s, and many people with Alzheimer’s carry no ε4 at all. An odds ratio is a shift in probability, not a sentence. See does APOE4 shorten your life.
• These are averages from specific populations. They were measured largely in European-ancestry, clinic-based cohorts, and do not transfer perfectly to any one person.
• Ancestry matters a lot. The ε4 association is notably weaker in people of African ancestry, for example, and varies elsewhere too. Age and sex shift it as well: the ε4 effect appears stronger in women in midlife (see women and sex differences).

Common questions

What is the difference between 3/4 and 4/4? Both carry ε4, but 4/4 means two copies, roughly a several-fold higher average risk than 3/4, plus an earlier average onset. The jump from one copy to two is real, which is why people search this comparison so often.

Is 2/4 good or bad? Genuinely mixed, and probably less reassuring than it sounds. The protective ε2 partly counters the ε4, but only partly: some studies put 2/4 risk closer to 3/4 than to the 3/3 average. Treat it as elevated, not neutralized.

Where does my genotype come from, and can I see it? From your two parents, one allele each. If you have consumer DNA data, you can often read it yourself. See find your APOE status in your 23andMe data.

What to do with your genotype

Whatever your pair, the action items converge on the same modifiable levers: cardiovascular health, exercise, diet, sleep, and metabolic health. If you carry one or two ε4 copies, the evidence suggests those levers may matter more, not less.

Knowing your genotype is a starting point for a conversation with a clinician or genetic counselor, not a diagnosis. See how to get tested. This is general education, not medical advice.