Also Known As
APOE e4
Formal Name
Apolipoprotein E Genotyping
This article was last reviewed on
This article waslast modified on March 15, 2019.

Were you looking instead for APOE genotyping ordered to evaluate for cardiovascular disease? If so, see APOE Genotyping, Cardiovascular Disease.

At a Glance
Why Get Tested?

APOE genotyping is not widely used. The clinical usefulness of this test is still being researched, but it may be used as an aid in the diagnosis of probable late onset Alzheimer disease (AD) in a symptomatic adult

When To Get Tested?

When you have progressive symptoms of dementia and your healthcare practitioner wants to determine the likelihood that this is due to AD

Sample Required?

A blood sample drawn from a vein

Test Preparation Needed?

No test preparation is usually needed. However, prior to testing, you may wish to receive genetic counseling. This could be a helpful and important step in deciding if testing is right for you and for dealing with the result if you decide to be tested.

You may be able to find your test results on your laboratory's website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab's website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called "normal" values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Apolipoprotein (Apo) E is produced under the direction of the APOE gene and is one of five main types of blood lipoproteins (A-E). This test evaluates a person's DNA to determine what combination of APOE forms (genotype) is present. The APOE gene exists in three different forms (alleles) – e2, e3, and e4 – with e3 being the most common allele, found in 60% of the general population. Everyone inherits a pair of APOE genes that is some combination of these three.

APOE e4 has been associated with an increased risk of late onset Alzheimer disease (AD), that is AD that develops after the age of 65. This effect is additive in that one copy of e4 (e2/e4 or e3/e4) carries some increased risk and two copies of e4 (e4/e4) are associated with even more of a risk of developing AD. It is important to note, however, that we are talking about the risk relative to other people at the same age with fewer copies of e4. In terms of lifetime risk, most individuals with APOE e4 will never develop AD and there are many people with AD who are e4 negative.

Accordion Title
Common Questions
  • How is it used?

    APOE genotyping is sometimes used as an added test to help in the diagnosis of probable late onset Alzheimer disease (AD) in symptomatic adults. However, the association of the e4 allele with late onset AD does not mean that it causes AD, only that more people with late onset AD have e4 alleles compared to similar aged peers without late onset AD. For this reason, APOE genotyping is referred to as susceptibility or risk factor testing since it indicates whether there is an increased risk of AD but is not specifically diagnostic of AD. For example, if a person has dementia, the presence of APOE e4 may increase the likelihood that the dementia is due to AD but does not prove that it is.

    There are no clear-cut tests to diagnose Alzheimer disease during life. Healthcare practitioners can, however, make a reasonably accurate clinical diagnosis of AD by ruling out other potential causes of dementia and checking for a genetic predisposition to AD with APOE genotyping as supplemental information in conjunction with tau protein and beta amyloid testing.

  • When is it ordered?

    APOE genotyping may sometimes be ordered when an individual has symptoms of progressive dementia, such as:

    • Loss of memory that affects daily life—forgetting information that was recently learned. This can occur with normal aging, but the information is usually remembered later. This includes forgetting important dates or events, having to rely on memory aids, and asking for the same information again and again.
    • Difficulty planning or problem solving, such as keeping track of bills and payments
    • Problems completing usual tasks, such as forgetting how to get to a familiar location
    • Confusion about place or time—losing track of time, forgetting where you are or how you got there
    • Increasing difficulty reading or judging distances
    • Problems speaking or writing—forgetting words, repeating the same thing, struggling with vocabulary
    • Losing things more frequently and not being able to logically retrace steps to find them
    • Impaired judgment, such as giving away unusually large amounts of money
    • Increasing withdrawal from activities, including social, work or family events
    • Changes in mood and personality, such as increasing anxiety, fear, suspicion and depression

    After non-AD causes, such as overmedication, vascular dementia (caused by strokes), and thyroid disease, have been ruled out, APOE genotyping may help determine the probability that dementia is due to Alzheimer disease.

  • What does the test result mean?

    People who have symptoms of Alzheimer disease (AD) and have one or more APOE e4 copies are more likely to have AD. However, it is not diagnostic of AD and should not be used to screen asymptomatic people or their family members. Many individuals who have APOE e4 alleles will never develop AD. Even in symptomatic people, only about 60% of those with late onset AD will have APOE e4 alleles.

    Although APOE genotyping may be used clinically by Alzheimer experts, it can only provide additional information about a person with dementia. A definite diagnosis of Alzheimer disease can only be made by examining a person's brain tissue after their death.

  • Can this test be done at my local lab?

    APOE genotyping is not available in every laboratory. If a healthcare practitioner recommends this test, the specimen will likely be sent to a reference laboratory and results may take longer to return than they would from a local laboratory.

  • My father has been diagnosed with probable late onset Alzheimer disease and his APOE genotype test is negative for e4 alleles. Should his doctor be doing other genetic testing?

    No, not at this time. Forty percent of individuals who have late onset Alzheimer disease (AD) are negative for APOE e4 alleles.

    Currently, there are only three known genes that are associated with AD. Mutations in each of these genes (PSEN1, PSEN2, and APP) are associated only with a rare and early onset form of AD. Changes to these genes are not associated with typical or late onset AD. If you have a strong family history of AD that includes multiple family members across several generations, you may want to talk to your doctor about genetic counseling for risk assessment.

  • Should everyone have their APOE genotype tested?

    No, the test is not intended to be used to screen the general population. It is intended to be used in very specific situations to give a healthcare practitioner additional information. The association of APOE's e4 allele with AD arose as part of the Framingham Heart study to evaluate genetic risk factors related to cardiovascular health.

  • Is there a reason to test for APOE genotype more than once?

    No, not unless your healthcare provider suspects that the first test was in error. A person inherits one copy of the gene from each parent and genotype does not change.

View Sources

Sources Used in Current Review

Martins, R. (2018 March 13). Alzheimer's Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies-Gains from AIBL and DIAN Cohort Studies. J Alzheimers Dis. 2018;62(3):965-992. Available online at https://www.ncbi.nlm.nih.gov/pubmed/29562546. Accessed February 2019.

Neu, S. et. al. (2017 October 1). Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis. JAMA Neurol. 2017 Oct 1;74(10):1178-1189. Available online at https://www.ncbi.nlm.nih.gov/pubmed/28846757. Accessed February 2019.

(© 2016). Genetic Testing. Alzheimer's association. Available online at https://www.alz.org/media/homeoffice/downloads/genetic_testing.pdf. Accessed February 2019.

(© 2018). Earlier Diagnosis. Alzheimer's association. Available online at https://www.alz.org/alzheimers-dementia/research_progress/earlier-diagnosis. Accessed February 2019.

(2018 October, Reviewed). APOE gene. Genetics Home Reference. Available online at https://ghr.nlm.nih.gov/gene/APOE. Accessed February 2019.

Berkowitz, d. et. al. (2018 October 15). Clinical Application of APOE in Alzheimer's Prevention: A Precision Medicine Approach. J Prev Alzheimers Dis. 2018; 5(4): 245–252. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188641/. Accessed February 2019.

Garg, S. (2015 February 21, Updated). Alzheimer Disease and APOE-4. Medscape Genomic Medicine. Available online at https://emedicine.medscape.com/article/1787482-overview#showall. Accessed February 2019.

Liao, F. (2017 February). Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease. Curr Opin Lipidol. 2017 Feb;28(1):60-6. Available online at https://www.ncbi.nlm.nih.gov/pubmed/27922847. Accessed February 2019.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Sloane, P. (1998, November 1). Advances in the Treatment of Alzheimer's Disease. American Family Physician by the American Academy of Family Physicians [On-line journal]. Available online at http://www.aafp.org/afp/981101ap/sloane.html.

Eastman, P. (2002 March). Keeping Alzheimer's at Bay, Early Diagnosis Keeps Patients Functioning Longer. AARP Bulletin Online [On-line serial]. Available online at http://www.aarp.org/bulletin/departments/2002/health/0310_health_1.html.

McConnell, S., et. al. Unraveling the Mysteries of Alzheimer's Disease: Exciting New Developments in Research. From panel sponsored by the Alzheimer's Association [On-line information]. Available online at http://www.asaging.org/am/cia2/alzheimer.html.

Galasko, D., et. al. (1998). High Cerebrospinal Fluid Tau and Low Amyloid b42 Levels in the Clinical Diagnosis of Alzheimer Disease and Relation to Apolipoprotein E Genotype. Arch Neurol [On-line journal], vol (55) pages (937-945). Available online at http://archneur.ama-assn.org/issues/v55n7/abs/noc7433.html.

ARF (1996-2002). Standard Medical Workup for Alzheimer's Disease. Alzheimer Research Forum [On-line information]. Available online at http://www.alzforum.org/members/research/treatment_guide/workup.html.

Family Caregiver Alliance. Fact Sheet: Alzheimer's Disease [On-line information]. Available online at http://www.caregiver.org/factsheets/diagnoses/alzheimersC.html.

Bird, T. (2001 June 22 last update). Alzheimer Overview. GeneReviews [On-line information]. Available online through http://www.genetests.org.

Gottlieb, F. and Lambert, J. G. (2002, January 2, last update). Alzheimer’s Disease. MedlinePlus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000760.htm.

Miller, M. (1998 February 18). 26 national Alzheimer's Disease Centers Collaborate on Study of the Utility of Genetic Testing for Alzheimer's. National Institutes of Health News Release [On-line press release]. Available online at http://www.nia.nih.gov/news/pr/1998/02%2D18.htm.

NIH (2000). Progress report on Alzheimer's disease, taking the next steps. NIH Publication No. 00-4859 [On-line report]. Available online at http://www.alzheimers.org/pubs/prog00.htm#Introduction.

UniSci (2002, April 08). New Approaches Seen For Early Alzheimer's Diagnosis. Daily University Science News [On-line Article]. Review of two studies found in Neuropsychology, Vol 16 (2). Available online at http://unisci.com/stories/20022/0408025.htm.

Eldercare (2002 February 28, last update). Is it Alzheimer's ... or Just Forgetfulness? Sponsored by Nebraska's Area Agencies on Aging [On-line information]. Available online at http://nncf.unl.edu/eldercare/info/lifeline/LLforget.html.

Hain, T. (2000 February 13). Alzheimer's Disease. Neurology, Northwestern University Medical School [3rd year neurology medical student curriculum material]. Available online at http://www.neuro.nwu.edu/meded/behavioral/alzheimers.html.

Kleiner-Fisman, G., Updated by (2002 January 2, last update). CSF Collection. MedlinePlus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm.

MEDLINEplus, (2001 November 20). Familial dysbetalipoproteinemia. MedlinePlus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000402.htm.

Eichner, J., et. al. (2002, March 15). Apolipoprotein E Polymorphism and Cardiovascular Disease. HuGE Review, appeared in Am J Epidemiol 2002 [On-line journal], 155(6): 487-95. Available online at http://www.cdc.gov/genomics/hugenet/reviews/APOEcardio.htm.

MEDLINEplus, (2001 October 29). Familial hypercholesterolemia. MedlinePlus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000392.htm.

Stephen P. Day, Ph.D. Director, Medical Affairs, Third Wave Molecular Diagnostics.

Robert C. Green, M.D., M.P.H. Professor of Neurology, Genetics and Epidemiology. Director, Alzheimer's Disease Clinical and Research Program. Boston University Schools of Medicine and Public Health, Boston, MA.

Ian R.A. Mackenzie, MD FRCPC. Department of Pathology, Vancouver General Hospital, British Columbia, Canada.

Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 110-114.

(Updated 2009 May 9). Alzheimer's Disease Genetics Fact Sheet. Alzheimer’s Disease Education & Referral Center [On-line information]. Available online at http://www.nia.nih.gov/Alzheimers/Publications/geneticsfs.htm. Accessed May 2009.

Bird, T. (Revised 2008 July 24). Alzheimer Disease Overview. GeneReviews [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene∂=alzheimer. Accessed May 2009.

Rogaeva, E. (2009 February 5). The Genetic Profile of Alzheimer's Disease: Updates and Considerations. Medscape from Geriatrics and Aging [On-line information]. Available online at http://www.medscape.com/viewarticle/586756. Accessed May 2009.

Gandelman, G. (Updated 2008 January 23). Familial dysbetalipoproteinemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000402.htm. Accessed May 2009.

Mayo Clinic Staff (2008 September 17). Alzheimer's: Is it in your genes? MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/print/alzheimers-genes/AZ00047/METHOD=print. Accessed May 2009.

(Updated 2008 December). Cardiovascular Disease (Non-traditional Risk Markers) - Risk Markers - CVD (Non-traditional). ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/CardiacDz/CVDRiskMarkerNontrad.html. Accessed May 2009.

(September 18, 2007) Riordan M. Linear association among apoE genotypes with LDL levels and coronary risk. Available online at http://www.theheart.org/article/813529.do. Accessed July 2009.

Small, G. (Updated 2012 February 8). Alzheimer Disease and APOE-4. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1787482-overview#showall. Accessed March 2014.

Anderson, H. (Updated 2014 March 3). Alzheimer Disease. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1134817-overview. Accessed March 2014.

(© 2014) What We Know Today About Alzheimer's Disease. Alzheimer’s Association [On-line information]. Available online at http://www.alz.org/research/science/alzheimers_disease_causes.asp#chromosomes. Accessed March 2014.

(2013 January 14). 2011-2012 Alzheimer's Disease Progress Report. Alzheimer's Disease Education and Referral Center [On-line information]. Available online at http://www.nia.nih.gov/alzheimers/publication/2011-2012-alzheimers-disease-progress-report/. Accessed March 2014.

(Reviewed 2012 December). Alzheimer's Disease. NIHSeniorHealth [On-line information]. Available online at http://nihseniorhealth.gov/alzheimersdisease/whatisalzheimersdisease/01.html. Accessed March 2014.

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