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APOE Genotype

A DNA test that shows which versions of the APOE gene you carry (e2, e3 or e4). The e4 version is linked to higher odds of late-onset Alzheimer's disease, but it does not mean you will get it.

AI-verified against cited sources. Awaiting expert reviewAlso called APOE, ApoE, APOE4LOINC 42315-2

What it is

APOE is a gene that makes a protein that helps carry cholesterol and other fats in your blood and brain. You inherit one copy of the gene from each parent, and each copy comes in one of three common versions: e2, e3 or e4. That gives six possible pairs, from e2/e2 to e4/e4. The e3 version is the most common, found in about 78 of every 100 gene copies worldwide, while e4 is found in about 14 and e2 in about 8. Labs read two spots in your DNA (named rs429358 and rs7412) to work out your pair. Some labs report only whether you carry e4 and how many copies.

Why it matters

APOE is the strongest common genetic factor linked to late-onset Alzheimer's disease. The e4 version raises the odds, and two copies raise them more. The e2 version is linked to lower odds. These are odds across groups of people, not a prediction for you: many people with e4 never develop Alzheimer's disease, and not everyone with Alzheimer's disease carries e4. APOE also affects how the body handles cholesterol, and two copies of e2 are linked to an uncommon lipid condition called type III hyperlipoproteinemia. Because the result cannot say what will happen to you, a 2011 joint guideline from the American College of Medical Genetics and the National Society of Genetic Counselors says APOE testing is not clinically recommended for predicting Alzheimer's risk, and it advises against direct-to-consumer APOE testing. If you do have a result, a genetic counselor or your clinician can help you think it through.

If it’s high

Carrying one or two copies of e4 (e3/e4, e2/e4 or e4/e4) is linked to higher odds of late-onset Alzheimer's disease than the most common pair, e3/e3. In a large pooled analysis of white participants, the odds were about 3 times higher with e3/e4 and about 15 times higher with e4/e4. These are group averages, and the link was weaker in some other ancestry groups and stronger in others. Many people who carry e4 never develop Alzheimer's disease. An e4 result is not a diagnosis, and it does not tell you whether or when symptoms might start.

Common causes

  • Inherited from one or both parents, one gene copy from each
  • Common: roughly 1 in 4 people carry at least one e4 copy (worked out from the worldwide e4 frequency of about 14 in 100 gene copies)

What can help

  • Talk with a clinician or genetic counselor about what the result does and does not mean before you share it widely
  • Ask which everyday habits support heart and brain health in general
  • Ask how a result could affect life, disability or long-term care insurance, since legal protections in the US have limits
  • If you or someone close to you notices memory or thinking changes, ask for a proper evaluation, because an APOE result cannot say whether symptoms come from Alzheimer's disease

What can affect your result

  • Your genotype is fixed at birth, so age, food, medicines, fasting and time of day do not change it
  • Ancestry: in one large analysis, the link between e4 and Alzheimer's disease was weaker in African American and Hispanic participants and stronger in Japanese participants than in white participants
  • Age and sex: the e4 link was seen from age 40 to 90, gets weaker after about 70, and differs by sex
  • A past bone marrow or stem cell transplant from a donor can interfere with DNA tests run on blood
  • A previous bone marrow or stem cell transplant from a donor can interfere with DNA tests run on blood, because the DNA may come from the donor's cells.
  • Most labs read the DNA directly (genotyping). Some labs report the same six pairs from a protein method on plasma (mass spectrometry, called an ApoE proteotype), which reads the protein instead of the DNA.

Your APOE genotype is fixed at birth and does not change.

When to talk to a clinician

A genotype result is not an emergency. See a clinician if you or someone close to you notices memory or thinking changes that get in the way of daily life. An APOE result alone cannot say whether those changes come from Alzheimer's disease.

Questions you could ask

  • Does it make sense for me to have this test at all, given my situation?
  • How could this result affect insurance, such as long-term care or life insurance?
  • If my result includes e2/e2, is it worth checking my cholesterol and triglycerides?
  • What does an e4 result mean for me, given my age and family history?
  • Would it help to talk with a genetic counselor about this result?
  • Who in my family might this result matter to, and how should I share it?

Questions people ask

Does having e4 mean I will get Alzheimer's disease?

Not necessarily. The e4 version raises the odds, and two copies raise them much more than one. Many people with one copy never develop Alzheimer's disease, and some people without e4 do. A 2024 study found that nearly all people with two copies had Alzheimer's-related changes on biomarker tests by about age 65, which is not the same as having symptoms. Age and other genes also play roles, so a clinician cannot predict your outcome from this result alone.

Is it a good idea to get tested?

That is a personal choice. A 2011 joint guideline from the American College of Medical Genetics and the National Society of Genetic Counselors says APOE testing to predict Alzheimer's risk is not clinically recommended because it has limited usefulness and poor predictive value. It also advises against direct-to-consumer APOE testing. If you are thinking about it, talking with a genetic counselor first can help you decide and plan for how you would handle the result.

What does e3/e3 mean?

It is the most common pair. It means you carry neither e4 nor e2. It does not rule out Alzheimer's disease, which also happens in people without e4, and it does not mean you will develop it.

Why might a clinician check APOE before an Alzheimer's treatment?

People who carry e4, especially two copies, have a higher chance of changes on brain scans, such as swelling or small bleeds, with a newer kind of Alzheimer's medicine that clears amyloid from the brain. Appropriate-use recommendations for one of these medicines suggest APOE testing to help with that conversation. Only a clinician who knows your history can say whether any treatment fits you.

What does e2 mean?

e2 is the least common version and is linked to lower odds of Alzheimer's disease. Two copies (e2/e2) are linked to an uncommon lipid condition called type III hyperlipoproteinemia, which causes high cholesterol and triglycerides. Only a minority of people with e2/e2 develop it. In one review, about 15 in 100 did.

Show the science and sources

For clinicians and researchers

The APOE alleles are defined by two SNPs, rs429358 (c.388T>C on NM_000041) and rs7412 (c.526C>T), which give three protein isoforms that differ only at amino acids 112 and 158: ApoE2 has Cys112 and Cys158, ApoE3 has Cys112 and Arg158, and ApoE4 has Arg112 and Arg158 (Liu 2013). Worldwide allele frequencies are about 8.4% for e2, 77.9% for e3 and 13.7% for e4 (Liu 2013). In a pooled analysis of 5,930 patients and 8,607 controls, odds ratios for Alzheimer's disease compared with e3/e3 among white participants from clinic or autopsy studies were 0.6 (95% CI 0.2-2.0) for e2/e2, 0.6 (0.5-0.8) for e2/e3, 2.6 (1.6-4.0) for e2/e4, 3.2 (2.8-3.8) for e3/e4 and 14.9 (10.8-20.6) for e4/e4. The e4 association was weaker in African American and Hispanic cohorts and stronger in Japanese cohorts (e4/e4 odds ratio 33.1), was present from age 40 to 90 but diminished after age 70, and varied by sex (Farrer 1997). A 2024 analysis of 3,297 people with pathology data and 10,039 with clinical data reported that almost all e4 homozygotes had Alzheimer's pathology and higher biomarker levels from age 55, with symptom onset at age 65.1, earlier than in e3 homozygotes, and proposed that e4 homozygosity is a distinct genetic form of Alzheimer's disease (Fortea 2024). For e2/e2, about 15% develop familial dysbetalipoproteinemia, usually with secondary factors such as obesity and insulin resistance, and the condition is estimated at 0.12 to 0.40% of people depending on the definition (Koopal 2017). The ACMG and NSGC practice guideline states that testing for susceptibility loci such as APOE is not clinically recommended because of limited clinical utility and poor predictive value, and that direct-to-consumer APOE testing is not advised (Goldman 2011). The 2023 appropriate use recommendations for lecanemab note that e4 carriers, especially homozygotes, have a higher risk of amyloid-related imaging abnormalities (ARIA) and recommend APOE genotyping to inform risk discussions with candidates (Cummings 2023). LOINC 42315-2 lists the six pairs as its answer set. The same six pairs are reported as an ApoE proteotype by a plasma LC-MS/MS method (Mayo Clinic Laboratories and C2N Diagnostics PrecivityAD2 reflex), which reads the protein, not the DNA.

LOINC 42315-2 (primary), 21619-2, 104166-4, 34438-2. Specimen: whole-blood.

Sources

  1. APOE gene, MedlinePlus Genetics, National Library of Medicine
  2. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors, Genetics in Medicine (2011)
  3. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis, JAMA (1997)
  4. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy, Nature Reviews Neurology (2013)
  5. APOE4 homozygosity represents a distinct genetic form of Alzheimer's disease, Nature Medicine (2024)
  6. Lecanemab: Appropriate Use Recommendations, Journal of Prevention of Alzheimer's Disease (2023)
  7. Familial dysbetalipoproteinemia: an underdiagnosed lipid disorder, Current Opinion in Endocrinology, Diabetes and Obesity (2017)
  8. PrecivityAD2, Reflex to Apolipoprotein E, Plasma (test AD2AR), Mayo Clinic Laboratories / C2N Diagnostics (Extended Catalog, testcatalog.org)
  9. dbSNP record for rs429358 (APOE c.388T>C); rs7412 is c.526C>T (NCBI Variation Services API), NCBI dbSNP
  10. LOINC 42315-2 with answer list (NLM Clinical Tables API), National Library of Medicine / Regenstrief Institute

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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