The two genotypes side by side
Everyone has two copies of the APOE gene, one from each parent. "Heterozygous" means two different versions of a gene, "homozygous" two identical ones (NHGRI). Here, 3/4 is APOE3 plus APOE4, and 4/4 is two APOE4.
| One copy (3/4) | Two copies (4/4) | General population | |
|---|---|---|---|
| Develop Alzheimer's by age 85, men | about 23 in 100 | about 51 in 100 | about 11 in 100 |
| Develop Alzheimer's by age 85, women | about 30 in 100 | about 60 in 100 | about 14 in 100 |
These are lifetime risk estimates from 7,531 people with Alzheimer's and 10,132 controls of European ancestry, combined with US (Rochester) incidence rates (Genin, 2011). Women's estimates are higher than men's in every row.
What about 2/4? A 2/4 genotype also carries one APOE4 copy, but the 23 to 30 in 100 figures above do not apply to it. The Genin paper reports 2/4 as its own genotype group, so read that paper's table for it rather than borrowing the 3/4 numbers.
What the numbers say, and what they do not
- Two copies raise risk further than one. The authors call the pattern semi-dominant: one copy raises risk, and two copies raise it further (Genin, 2011; MedlinePlus).
- It is a risk, not a verdict. Even at the higher end, about 40 to 49 in 100 people with two copies do not develop Alzheimer's by 85 (100 minus 51 to 60). MedlinePlus puts it this way: people with the e4 allele inherit an increased risk of Alzheimer's disease, not the disease itself.
- The estimates move with the data. The same paper recalculated the estimates with French (PAQUID) incidence rates instead of US ones. At 85 that gave 35 in 100 for women with 3/4 and 68 in 100 for women with 4/4. Treat every number here as a range, not a prediction for one person.
- Earlier onset is possible with either genotype. Splitting the data by age group, the authors found APOE4 is a risk factor for early-onset as well as late-onset Alzheimer's (Genin, 2011). For the risk at each age, see risk by age.
How Phoenix members compare
Among Phoenix members with a known genotype, roughly half carry two copies, and Phoenix's founder, Kevin Tran, carries two. Phoenix's homepage reports 750+ APOE4 carriers and says 89% see improvement in key APOE4 biomarkers within 3 months. Phoenix only earns revenue from your membership, nothing else. Members with one copy and members with two copies are both part of the community.
Which one do you have?
Your genotype is written as a pair, for example 3/4, 2/4 or 4/4. APOE 3/4 meaning explains one copy in detail. If you are unsure what your report says, start with your APOE4 result.
How the gene passes between generations is covered in Is APOE4 inherited? on Field Notes, and the genetic testing and family guide covers talking to relatives.
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