APOE2 vs APOE3 vs APOE4: what is the difference?

By Dr. Kevin Tran, Doctor of Pharmacy · Last updated: October 24, 2026

APOE has three common versions, and they pull in different directions. APOE3 is the most common and is treated as the reference. APOE4 raises the chance of Alzheimer's disease and tends to raise LDL cholesterol. APOE2 lowers the chance of Alzheimer's and tends to lower LDL. You carry two copies, one from each parent, so your genotype is a pair such as 3/3, 3/4 or 2/3.

The three versions side by side

The three versions differ only at two positions in the protein, amino acids 112 and 158 (Liu, 2013), and the allele shares are worldwide figures from the same review. The Alzheimer's rows come from a review of the field (Liu, 2013), early family and case-control evidence for APOE2 being protective (Corder, 1994) and MedlinePlus. The LDL and heart rows come from a pooled analysis of 82 lipid studies (86,067 healthy people) and 121 coronary studies (Bennet, 2007).

What the genotype pair means

Your genotype combines the two versions you inherited, so there are six pairs: 2/2, 2/3, 2/4, 3/3, 3/4 and 4/4. Some practical readings:

• 3/3 is the most common pair and the usual comparison group in studies.

• 2/3 had the lowest Alzheimer's risk in the original 1994 study (Corder, 1994).

• 3/4 is one copy of APOE4. See APOE 3/4 meaning.

• 4/4 is two copies of APOE4, the highest-risk common pair.

• 2/4 is one copy of APOE2 and one copy of APOE4.

For absolute numbers by genotype and age, see Alzheimer's risk by age.

What each version does to cholesterol

APOE helps carry cholesterol in the blood and in the brain. Across 82 studies, the relationship between genotype and LDL cholesterol was roughly linear: people with 2/2 had about 31% lower mean LDL than people with 4/4, with the other pairs in between (Bennet, 2007). The same analysis found that coronary risk followed the same order. This is why Phoenix reads LDL and ApoB for carriers against specific targets. See the APOE4 LDL target.

Does it work the same in everyone?

Not exactly. A study of about 68,700 people from four ancestry groups found APOE4 linked to higher Alzheimer's risk in every group, with the strength differing between groups. APOE2 was linked to lower risk in White and Black participants, but no significant association was found in Hispanic or East Asian participants (Belloy, 2023). A genotype is one input; it is not a fixed number for everybody.

What to do with this

Know your pair first; a result looks like 3/4. Phoenix's genetic testing and family guide covers the options. Phoenix has 750+ APOE4 carriers, and 89% see improvement in key APOE4 biomarkers within 3 months.

Frequently asked questions

Which is worst, APOE4 or APOE2?

For Alzheimer's risk, APOE4 is the higher-risk version and APOE2 the lower-risk one. APOE2 is not simply good: it is linked to a rare lipid condition, type III hyperlipoproteinemia (MedlinePlus).

Is APOE3 "normal"?

It is the most common version and the usual reference in research, found in more than half of people (MedlinePlus). That makes it the baseline, not a guarantee.

Can I carry both APOE2 and APOE4?

Yes. A 2/4 genotype means one copy of each.

Do I inherit the version from my mother or father?

Both: one copy from each parent. See how APOE4 is inherited.

Is this medical advice?

No. Phoenix educates. A genetic counselor or doctor can advise on your result.

Sources

• Liu, Nat Rev Neurol 2013: Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy

• Bennet, JAMA 2007: Association of apolipoprotein E genotypes with lipid levels and coronary risk

• Corder, Nat Genet 1994: Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease

• Belloy, JAMA Neurol 2023: APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry

• MedlinePlus Genetics, APOE gene

If you carry APOE4, apply to join Phoenix (60-day money-back guarantee).

This is not medical advice. Phoenix educates. A genetic counselor or doctor can advise on your result.