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Genetics Home Reference: your guide to understanding genetic conditions
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APOE

Reviewed December 2008

What is the official name of the APOE gene?

The official name of this gene is “apolipoprotein E.”

APOE is the gene's official symbol. The APOE gene is also known by other names, listed below.

What is the normal function of the APOE gene?

The APOE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. Apolipoprotein E is a major component of a specific type of lipoprotein called very low-density lipoproteins (VLDLs). VLDLs remove excess cholesterol from the blood and carry it to the liver for processing. Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessels (cardiovascular diseases), including heart attack and stroke.

There are at least three slightly different versions (alleles) of the APOE gene. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population.

How are changes in the APOE gene related to health conditions?

Alzheimer disease - increased risk from variations of the APOE gene

The e4 version of the APOE gene increases an individual's risk for developing late-onset Alzheimer disease. People who inherit one copy of the APOE e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. The APOE e4 allele may also be associated with an earlier onset of memory loss and other symptoms.

It is not known how the APOE e4 allele is related to the risk of Alzheimer disease. However, researchers have found that this allele is associated with an increased number of protein clumps, called amyloid plaques, in the brain tissue of affected people. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of neurons and the progressive signs and symptoms of this disorder.

It is important to note that people with the APOE e4 allele inherit an increased risk of developing Alzheimer disease, not the disease itself. Not all people with Alzheimer disease have the APOE e4 allele, and not all people who have this allele will develop the disease.

other disorders - associated with the APOE gene

Variants of apolipoprotein E have been studied extensively as risk factors for many different conditions. For example, APOE alleles have been shown to influence the risk of cardiovascular diseases. People who carry at least one copy of the APOE e4 allele have an increased chance of developing atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. This progressive narrowing of the arteries increases the risk of heart attack and stroke.

The APOE e2 allele has been shown to greatly increase the risk of a rare condition called hyperlipoproteinemia type III. Most people with this disorder have two copies of the APOE e2 allele, leading researchers to conclude that the e2 allele plays a critical role in the development of the condition. Hyperlipoproteinemia type III is characterized by increased blood levels of cholesterol, certain fats called triglycerides, and molecules called beta-very low-density lipoproteins (beta-VLDLs), which carry cholesterol and lipoproteins in the bloodstream. A buildup of cholesterol and other fatty materials can lead to the formation of small, yellow skin growths called xanthomas and the development of atherosclerosis.

APOE gene variants have also been studied as a potential risk factor for age-related macular degeneration, an eye disease that is a leading cause of vision loss among older people worldwide. Some studies have suggested that having at least one copy of the APOE e4 allele may help protect against this disease or delay the onset of vision loss, while having at least one copy of the APOE e2 allele may increase the risk of this disease or cause symptoms to appear earlier. However, other studies have not found these associations. More research is needed to clarify what role, if any, APOE gene variants play in the development of age-related macular degeneration.

Where is the APOE gene located?

Cytogenetic Location: 19q13.2

Molecular Location on chromosome 19: base pairs 44,905,781 to 44,909,392

The APOE gene is located on the long (q) arm of chromosome 19 at position 13.2.

The APOE gene is located on the long (q) arm of chromosome 19 at position 13.2.

More precisely, the APOE gene is located from base pair 44,905,781 to base pair 44,909,392 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about APOE?

You and your healthcare professional may find the following resources about APOE helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the APOE gene or gene products?

  • Apo-E
  • APOE_HUMAN
  • Apolipoproteins E

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding APOE?

allele ; amyloid ; apolipoprotein ; arteries ; atherosclerosis ; cardiovascular ; cholesterol ; gene ; heart attack ; lipoprotein ; low-density lipoproteins ; peptide ; population ; protein ; risk factors ; tissue ; toxic ; triglycerides

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ashford JW. APOE genotype effects on Alzheimer's disease onset and epidemiology. J Mol Neurosci. 2004;23(3):157-65. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15181244?dopt=Abstract)
  • Baird PN, Richardson AJ, Robman LD, Dimitrov PN, Tikellis G, McCarty CA, Guymer RH. Apolipoprotein (APOE) gene is associated with progression of age-related macular degeneration (AMD). Hum Mutat. 2006 Apr;27(4):337-42. (http://www.ncbi.nlm.nih.gov/pubmed/16453339?dopt=Abstract)
  • Bojanowski CM, Shen D, Chew EY, Ning B, Csaky KG, Green WR, Chan CC, Tuo J. An apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation. Environ Mol Mutagen. 2006 Oct;47(8):594-602. (http://www.ncbi.nlm.nih.gov/pubmed/16823865?dopt=Abstract)
  • Deary IJ, Whiteman MC, Pattie A, Starr JM, Hayward C, Wright AF, Carothers A, Whalley LJ. Cognitive change and the APOE epsilon 4 allele. Nature. 2002 Aug 29;418(6901):932. Erratum in: Nature 2002 Oct 3;419(6906):450. (http://www.ncbi.nlm.nih.gov/pubmed/12198535?dopt=Abstract)
  • Eichner JE, Dunn ST, Perveen G, Thompson DM, Stewart KE, Stroehla BC. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol. 2002 Mar 15;155(6):487-95. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11882522?dopt=Abstract)
  • Feussner G, Piesch S, Dobmeyer J, Fischer C. Genetics of type III hyperlipoproteinemia. Genet Epidemiol. 1997;14(3):283-97. (http://www.ncbi.nlm.nih.gov/pubmed/9181357?dopt=Abstract)
  • Heeren J, Beisiegel U, Grewal T. Apolipoprotein E recycling: implications for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):442-8. Epub 2005 Dec 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16373604?dopt=Abstract)
  • Hill JM, Bhattacharjee PS, Neumann DM. Apolipoprotein E alleles can contribute to the pathogenesis of numerous clinical conditions including HSV-1 corneal disease. Exp Eye Res. 2007 May;84(5):801-11. Epub 2006 Sep 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17007837?dopt=Abstract)
  • Huang Y. Apolipoprotein E and Alzheimer disease. Neurology. 2006 Jan 24;66(2 Suppl 1):S79-85. (http://www.ncbi.nlm.nih.gov/pubmed/16432152?dopt=Abstract)
  • Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5644-51. Epub 2006 Mar 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16567625?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/348)
  • Raber J, Huang Y, Ashford JW. ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging. 2004 May-Jun;25(5):641-50. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15172743?dopt=Abstract)
  • Rocchi A, Pellegrini S, Siciliano G, Murri L. Causative and susceptibility genes for Alzheimer's disease: a review. Brain Res Bull. 2003 Jun 30;61(1):1-24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12788204?dopt=Abstract)
  • Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11274343?dopt=Abstract)
  • Song Y, Stampfer MJ, Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med. 2004 Jul 20;141(2):137-47. (http://www.ncbi.nlm.nih.gov/pubmed/15262670?dopt=Abstract)
  • Tikellis G, Sun C, Gorin MB, Klein R, Klein BE, Larsen EK, Siscovick DS, Hubbard LD, Wong TY. Apolipoprotein e gene and age-related maculopathy in older individuals: the cardiovascular health study. Arch Ophthalmol. 2007 Jan;125(1):68-73. (http://www.ncbi.nlm.nih.gov/pubmed/17210854?dopt=Abstract)
  • van der Flier WM, Schoonenboom SN, Pijnenburg YA, Fox NC, Scheltens P. The effect of APOE genotype on clinical phenotype in Alzheimer disease. Neurology. 2006 Aug 8;67(3):526-7. (http://www.ncbi.nlm.nih.gov/pubmed/16894123?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2008
Published: April 17, 2014