What Does My APOE Genotype Mean? From e2/e2 to e4/e4

An APOE result may come from a consumer DNA report, a clinical lab (“APOE genotype: ε3/ε4”) or a cardiology panel that lists “ApoE 2/2” beside your cholesterol. Either way, the two numbers are the whole result, and what they mean depends on the pair.

This guide goes genotype by genotype: how common each is, how it changes the odds of Alzheimer’s disease, how ancestry and sex shift those numbers, and what to do next. For how the APOE protein works in the brain, see what APOE4 is and how it affects the brain.

The Short Answer

Your APOE genotype is the pair of APOE variants you inherited, one from each parent. e3/e3 is the most common genotype and the reference point for every risk figure.¹ Each e4 copy raises the odds of Alzheimer’s disease: in white populations, e3/e4 roughly triples them and e4/e4 raises them about 13- to 15-fold. The e2 variant lowers them.^2,3

The essential limitation: none of these genotypes is a diagnosis. The e4 effect is weaker in Black and Hispanic people,³ and even for e4/e4, one model put the lifetime risk of Alzheimer’s dementia by age 85 at 51 percent for men and 60 percent for women, not 100 percent.⁴

What Do the Two Numbers in an APOE Result Mean?

The APOE gene comes in three common versions, called alleles: e2, e3 and e4. You inherit one from each parent, which gives six possible pairs: e2/e2, e2/e3, e2/e4, e3/e3, e3/e4 and e4/e4. The order does not matter: e3/e4, e4/e3, “ε3/ε4” and “APOE 3/4” are the same result.

Check that your report names both alleles. Some consumer reports say only whether you carry e4, and without the second allele you cannot tell e3/e4 from e2/e4, which carry different risks.

How Common Is Each APOE Genotype?

In a Danish general-population study of 104,537 adults, 55.6 percent were e3/e3, 25.5 percent e3/e4, 12.4 percent e2/e3, 2.9 percent e2/e4, 2.9 percent e4/e4 and 0.7 percent e2/e2.¹ These shares differ by ancestry, because the frequency of the e4 allele ranges from about 9 to 30 percent across human populations.⁴

The table adds each genotype’s odds of Alzheimer’s disease from the 1997 Farrer meta-analysis of 5,930 patients and 8,607 controls² and the 2023 Belloy study of 68,756 people, which broke results down by ancestry.³

Two more ancestry groups change the picture. In Hispanic participants, the odds were 1.9 for e3/e4 and 3.6 for e4/e4, and e2 showed no significant protection.³ In East Asian participants, e3/e4 carried higher odds than in any other group, at 4.5;³ the Farrer analysis found 5.6 for e3/e4 and 33.1 for e4/e4 in Japanese participants.²

Why Doesn’t an Odds Ratio of 13 Mean You Are 13 Times More Likely to Get Alzheimer’s?

An odds ratio compares how often a genotype turns up in people with Alzheimer’s versus people without it, relative to e3/e3. It is not your chance of developing the disease. That is absolute risk, which starts from how common Alzheimer’s is.

One study converted APOE odds into lifetime risk for people of European ancestry. By age 85, the risk of Alzheimer’s disease regardless of genotype was 11 percent for men and 14 percent for women. For e3/e4 it was 23 percent for men and 30 percent for women. For e4/e4 it was 51 percent for men and 60 percent for women.⁴ Using French incidence data instead, the figures for women rose to 35 percent for e3/e4 and 68 percent for e4/e4.⁴ In this model, roughly 4 to 5 in 10 people with e4/e4 who reach 85 would not have developed Alzheimer’s dementia.

Shorter windows look smaller. In the Danish study, the 10-year risk of Alzheimer’s disease for people with e4/e4 was 7 percent for women and 6 percent for men in their sixties, 16 and 12 percent in their seventies, and 24 and 19 percent from age 80.¹

Other genes shift these numbers too. In the Rotterdam Study, among people with e4/e4, those with the highest-risk set of 23 other Alzheimer’s-linked gene variants had a 27-percentage-point higher risk of Alzheimer’s by 85 than those with the lowest-risk set, a difference of 7 to 10 years in age at onset.⁵

What Does e3/e3 Mean?

e3/e3 is the most common genotype, carried by just over half of people in the Danish study,¹ and the baseline for every comparison. It means average genetic risk from APOE, not low risk.

About 50 to 70 percent of people with Alzheimer’s carry at least one e4 allele, which means a large minority do not.⁶ Family history still counts: a person without e4 who has a parent or sibling with Alzheimer’s has an estimated 2 to 4 times the general population’s lifetime risk.⁶

What Does e3/e4 Mean?

e3/e4 means one copy of e4, carried by about one in four people in the Danish study.¹ Compared with e3/e3, the odds of Alzheimer’s were 3.2 in white participants in 1997² and 3.5 in 2023, against 2.2 in Black participants and 1.9 in Hispanic participants.³ In absolute terms, the estimated lifetime risk by 85 was 23 to 30 percent,⁴ so most people with e3/e4 do not develop Alzheimer’s dementia by that age.

Sex matters most for this genotype. In a meta-analysis of nearly 58,000 non-Hispanic white participants, men and women with e3/e4 had similar odds across ages 55 to 85 (3.09 and 3.31). Between 65 and 75, women’s odds were higher: 4.37 against 3.14 for men.⁷ The 2023 Belloy study found the same pattern at ages 60 to 70 and replicated it in Black and Hispanic participants.³

If you have e3/e4 and no symptoms, the practical sequence is laid out in what to do next if you carry APOE4.

What Does e4/e4 Mean?

e4/e4 means two copies of e4, one from each parent. It is uncommon: 2.9 percent of the Danish study population,¹ and roughly 2 percent of people of European ancestry by another estimate.⁴ It carries the highest odds of any genotype: about 13 to 15 times those of e3/e3 in white people, 6.5 in Black people and 3.6 in Hispanic people.^2,3

In 2024, a study in Nature Medicine argued that e4/e4 should be considered a distinct, genetically determined form of Alzheimer’s disease. The researchers analyzed brain autopsy data from 3,297 people and clinical and biomarker data from 10,039. Almost all people with e4/e4 showed Alzheimer’s pathology, and their biomarker levels were higher than those of e3/e3 from age 55. By 65, nearly all had abnormal amyloid in spinal fluid and 75 percent had a positive amyloid PET scan. Symptoms began at an average age of 65.1, earlier than in e3/e3 and within a narrower range.⁸

The study used research-cohort convenience samples that may not represent the general population, and the authors called for more diverse studies.⁸ In practice, e4/e4 warrants an earlier, more thorough evaluation, not a conclusion that the outcome is settled.

What Does e2/e4 Mean?

e2/e4 combines one risk-raising copy and one protective copy, and its risk falls between e3/e3 and e3/e4. It was 2.9 percent of the Danish study population.¹ For anti-amyloid drug safety it counts as one copy of e4. The odds of Alzheimer’s compared with e3/e3 were 2.6 in white participants in 1997,² and 2.2 in white, 1.6 in Black and 1.1 (not significant) in Hispanic participants in 2023.³ The Belloy authors noted that in East Asian and Hispanic participants, e2 appeared protective mainly when paired with e4.³

What Do e2/e3 and e2/e2 Mean?

e2/e3 is the second most protective genotype and the third most common, at 12.4 percent in the Danish study.¹ Its odds of Alzheimer’s were about 0.5 to 0.6 times those of e3/e3 in white participants and 0.69 in Black participants. There was no significant protection in Hispanic or East Asian participants.^2,3 In one meta-analysis the effect was stronger in women (odds 0.51) than in men (0.71).⁷

e2/e2 is the rarest genotype, at 0.7 percent.¹ In a 2020 study of more than 5,000 people whose diagnoses were confirmed at autopsy, e2/e2 carried odds of Alzheimer’s dementia 0.13 times those of e3/e3 and 0.004 times those of e4/e4. In clinically diagnosed cases without autopsy, the protection was smaller, at 0.52.⁹ Because so few people have e2/e2, estimates are imprecise: the 1997 meta-analysis could not show a significant effect,² and in the Danish population study, e2/e2 had a slightly higher 10-year risk of Alzheimer’s than e2/e3 and e3/e3.¹ It is probably the lowest-risk genotype, on thinner evidence than for e4.

e2/e2 also matters for your heart. Most people with familial dysbetalipoproteinemia (type III hyperlipoproteinemia) have e2/e2. About 15 percent of people with e2/e2 develop it, and it is associated with second factors such as obesity and insulin resistance. It raises both cholesterol and triglycerides, increases the risk of premature cardiovascular disease, and is treatable.¹⁰ If your APOE result came from a lipid or cardiology work-up, this is often why it was ordered.

How Does APOE Genotype Affect the Safety of Alzheimer’s Drugs?

APOE matters if you are ever considered for an anti-amyloid antibody such as lecanemab (Leqembi) or donanemab (Kisunla). These drugs can cause amyloid-related imaging abnormalities (ARIA), which are swelling or small bleeds in the brain seen on MRI. In a lecanemab trial reported in the drug’s FDA label, ARIA of either type occurred in 45 percent of treated e4/e4 patients, 19 percent of patients with one e4 copy and 13 percent of noncarriers. The FDA label says APOE e4 status should be tested before treatment starts.¹¹ For eligibility and how ARIA is monitored, see who qualifies for Leqembi and Kisunla, and how APOE4 changes ARIA risk.

Does It Matter Whether Your Result Came From 23andMe or a Clinical Lab?

It can. If a medical or financial decision will rest on a consumer result, confirm it in a clinical laboratory, with counseling before and after. The joint practice guideline of the American College of Medical Genetics and the National Society of Genetic Counselors advises against direct-to-consumer APOE testing and recommends genetic counseling for anyone tested.⁶ The guideline predates blood biomarkers and anti-amyloid drugs.

Know the insurance gap first. In the United States, the Genetic Information Nondiscrimination Act (GINA) bars health insurers and employers from using genetic information. Its protections do not cover life insurance, disability insurance or long-term care insurance, although some states add their own protections.¹² If you may want those policies, consider applying before testing.

Testing children is not recommended. The same guideline states that pediatric testing for Alzheimer’s disease should not occur.⁶ For how clinical testing and counseling work, see APOE testing with pre- and post-test counseling.

What Should You Do With Your APOE Result?

The genotype is fixed. What you do with it depends on which one it is:

• e3/e3 or e2/e3: Keep up standard prevention (blood pressure, blood sugar, sleep, hearing, exercise). Family history still counts.
• e3/e4 or e2/e4: Get a baseline evaluation of cognition, vascular and metabolic risk, and sleep, then work on what is modifiable.
• e4/e4: Seek the same evaluation, earlier and in more depth, and ask about prevention trials open to people with two copies.
• e2/e2: Ask for a full lipid panel if you have not had one, because of the link to dysbetalipoproteinemia.
• Any consumer result: Confirm it clinically before acting on it, and settle insurance questions first.

Common Questions

Is e3/e3 a good APOE result?

It is the most common, average result. It does not raise risk the way e4 does, but it is not protective: many people with Alzheimer’s have no e4 copy.

Does e3/e4 mean I will get Alzheimer’s disease?

No. One copy of e4 roughly triples the odds in white populations and raises them less in Black and Hispanic populations.^2,3 Estimated lifetime risk by age 85 is about 23 to 30 percent, so most people with e3/e4 do not develop Alzheimer’s dementia by then.⁴

Is e4/e4 the same as inherited early-onset Alzheimer’s?

Not quite. Early-onset familial Alzheimer’s is caused by rare mutations in the APP, PSEN1 and PSEN2 genes.⁶ Researchers have proposed that e4/e4 is also a genetic form of the disease because Alzheimer’s biology is nearly universal by the mid-sixties.⁸ But the lifetime risk of dementia is lower, at roughly 51 to 68 percent by 85 in published estimates.⁴

Can my APOE genotype change over time?

No. It is set at conception, so one accurate result is enough. What can change is the rest of your risk: blood pressure, metabolic health, sleep.

Why did my cardiologist order an APOE test?

Usually to look for familial dysbetalipoproteinemia, a treatable lipid disorder that most often occurs with e2/e2 and raises both cholesterol and triglycerides.¹⁰ The result also carries Alzheimer’s risk information.

Should my children or siblings be tested?

Testing children is not recommended; they can choose for themselves as adults.⁶ Adult siblings may have a different genotype, because each child inherits one of two alleles from each parent; they should decide with counseling and the insurance gap in mind.

Is an “ApoE3 blood test” the same as an APOE genotype?

Usually, yes. An “apo E3” or “APOE gene” test generally means the genotype test, done on blood or saliva. It is not the same as ApoB or ApoA1, which are protein levels on a lipid panel.

The Bottom Line

An APOE result is two numbers, and the pair matters more than either one. e3/e3 is average. Each e4 copy raises risk, more in some ancestries than others. e2 lowers it, and e2/e2 also deserves a lipid check. Even the highest-risk genotype is a probability, shaped by other genes, age, sex and modifiable risk factors.

The next step is the same for nearly everyone: confirm the result, read it against your ancestry and family history, and use it to decide how early to work on the risks you can change.

---

Dr. Nadir Bilici, MD, DipIBLM, is a board-certified neurologist (ABPN) and Diplomate of the International Board of Lifestyle Medicine specializing in preventive neurology, Alzheimer’s prevention, and cognitive risk assessment. He sees patients by telehealth in the states where he is licensed, with in-person appointments available on a select basis.

References

1. Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study. CMAJ. 2018;190(35):E1033-E1041. doi:10.1503/cmaj.180066
2. Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA. 1997;278(16):1349-1356. doi:10.1001/jama.1997.03550160069041
3. Belloy ME, Andrews SJ, Le Guen Y, et al. APOE genotype and Alzheimer disease risk across age, sex, and population ancestry. JAMA Neurol. 2023;80(12):1284-1294. doi:10.1001/jamaneurol.2023.3599
4. Genin E, Hannequin D, Wallon D, et al. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry. 2011;16(9):903-907. doi:10.1038/mp.2011.52
5. van der Lee SJ, Wolters FJ, Ikram MK, et al. The effect of APOE and other common genetic variants on the onset of Alzheimer's disease and dementia: a community-based cohort study. Lancet Neurol. 2018;17(5):434-444. doi:10.1016/S1474-4422(18)30053-X
6. Goldman JS, Hahn SE, Catania JW, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011;13(6):597-605. doi:10.1097/GIM.0b013e31821d69b8
7. Neu SC, Pa J, Kukull W, et al. Apolipoprotein E genotype and sex risk factors for Alzheimer disease: a meta-analysis. JAMA Neurol. 2017;74(10):1178-1189. doi:10.1001/jamaneurol.2017.2188
8. Fortea J, Pegueroles J, Alcolea D, et al. APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease. Nat Med. 2024;30(5):1284-1291. doi:10.1038/s41591-024-02931-w
9. Reiman EM, Arboleda-Velasquez JF, Quiroz YT, et al. Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun. 2020;11(1):667. doi:10.1038/s41467-019-14279-8
10. Koopal C, Marais AD, Visseren FLJ. Familial dysbetalipoproteinemia: an underdiagnosed lipid disorder. Curr Opin Endocrinol Diabetes Obes. 2017;24(2):133-139. doi:10.1097/MED.0000000000000316
11. Eisai Inc. LEQEMBI (lecanemab-irmb) prescribing information. Revised July 2026. DailyMed, U.S. National Library of Medicine. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9d1ff786-e577-410a-a273-c4d7d0e4e975
12. National Human Genome Research Institute. Genetic discrimination. Updated January 6, 2022. genome.gov/about-genomics/policy-issues/Genetic-Discrimination

Written and medically reviewed by Nadir Bilici, MD, DipIBLM. Published October 2026 · Medically reviewed on October 22, 2026. See our editorial policy.