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What is APOE, how is it related to Alzheimer's disease, and should I get tested too?

Zöe Powis, MS, CGC and Khalida Liaquat, MS, CGC

In a recent Vanity Fair article, an actor discusses his experience learning he is at an increased risk to develop Alzheimer’s disease (1). Since then, the media has been full of articles, podcasts, and blog pieces about dementia, APOE, and Alzheimer’s disease.  If you are thinking about testing to determine the genetic risk for developing Alzheimer’s disease, it is important to have some background information. 

What is APOE4?

Apolipoprotein E, or APOE, is a gene that comes in several forms, or alleles: APOE2, APOE3, and APOE4. Everyone carries 2 copies of this gene, one from each of their biological parents. Which APOE type you have, differentially impacts your risk for Alzheimer’s disease. APOE2 has been shown to reduce the risk for a person to develop Alzheimer’s disease1. APOE3 is most common and does not impact the risk for Alzheimer’s disease at all. In contrast, when someone has copies of APOE4, they have a higher chance of developing Alzheimer’s disease2,3. None of these APOE genetic results are absolute or even diagnose Alzheimer’s disease. They only give someone a higher or lower risk.

Since a person has 2 copies of APOE (1 from the egg and 1 from the sperm), they can have several different APOE combinations. The actor shared that he has 2 copies of APOE4 (also called homozygous for APOE4). Someone with two APOE4 copies has the highest risk of developing Alzheimer’s disease, but the risk is not 100%. Other factors, such as the environment, age, family history, and brain injury can influence someone’s risk. It is important to speak to a healthcare provider to understand your risk.

What is Alzheimer’s disease and dementia?

While many people “know” what Alzheimer’s disease is, fully understanding it can help to understand your risk. Alzheimer’s disease affects more than 6 million people each year. It is a progressive condition of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. Alzheimer’s disease usually occurs in people older than 65 (called late onset), but less common forms of the disease appear earlier in adulthood (early onset). It is important to note that Alzheimer’s disease is only 1 of several types of dementia. Many people use the term Alzheimer’s disease to describe family members with any form of dementia. Some dementias can be caused by treatable factors, such as depression, cancers, substance abuse, or vitamin deficiencies (4). Knowing from a medical provider the type of dementia and knowing the age of onset of symptoms is helpful in determining the risk for their family members to develop dementia. Someone may have a family member with dementia and/or Alzheimer’s disease and may or may not be at higher risk for developing the same condition.

Should I get tested?

If you or your patients are considering genetic testing to learn your risk of Alzheimer’s disease, the best place to start is with a genetic counselor. The genetic counselor will take your family history, ask personal health questions, and use all that information to talk about the best testing options and whether testing for APOE will give you the information you are seeking. In addition, they may discuss testing such as Quest’s AD-Detect to access the possibility of having Alzheimer disease for individuals with mild cognitive impairment or dementia testing. The actor shared that both he and his family still have questions about his test results. A genetic counselor will also help you understand your results, what they mean to you and your family.

To find a genetic counselor, visit the National Society of Genetic Counselors website to find someone near you or for virtual counseling. In addition, The National Society of Genetic Counselors has published guidelines on testing for Alzheimer disease 5.

If you have questions about genetic testing at Athena Diagnostics, you can call 1.866.GENE.INFO (1.866.436.3463) to speak to a genetic counselor or visit Athena Diagnostics. For more information about Alzheimer’s disease visit the Alzheimer's Association.


  1. Breznican, A. Chris Hemsworth Changed His Life After an Ominous Health Warning. Vanity Fair. November 17, 2022.
  2. Rebeck GW, Kindy M, LaDu MJ. Apolipoprotein E and Alzheimer's disease: the protective effects of ApoE2 and E3. J Alzheimers Dis. 2002 Jun;4(3):145-54. doi: 10.3233/jad-2002-4304.
  3. Sienski G, Narayan P, Bonner JM, et al. APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia. Sci Transl Med. 2021 Mar 3;13(583):eaaz4564. doi: 10.1126/scitranslmed.aaz4564. PMID: 33658354; PMCID: PMC8218593.
  4. Reiman EM, Caselli RJ, Chen K, et al. Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3334-9. doi: 10.1073/pnas.061509598. PMID: 11248079; PMCID: PMC30654.
  5. Bird TD, Miller BL. Alzheimer's disease and primary dementias. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 17 ed. New York, NY: McGraw-Hill; 2008:2393-406.
  6. Goldman JS, Hahn SE, Catania JW, et al. ADDENDUM: 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. 2019 Oct;21(10):2404. doi: 10.1038/s41436-019-0559-1. PMID: 31217590.