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APOE gene
URL of this page: https://medlineplus.gov/genetics/gene/apoe/

APOE gene

apolipoprotein E

Normal Function

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. 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.

Health Conditions Related to Genetic Changes

Alzheimer's disease

The e4 version of the APOE gene increases an individual's risk for developing late-onset Alzheimer's disease. Alzheimer's disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. The late-onset form of the condition occurs in people older than age 65. 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 compared to individuals with Alzheimer's disease who do not have this allele.

It is not known how the APOE e4 allele is related to the risk of Alzheimer's 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 amyloid plaques may lead to the death of nerve cells (neurons) and the progressive signs and symptoms of Alzheimer's disease.

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

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Age-related hearing loss

MedlinePlus Genetics provides information about Age-related hearing loss

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Age-related macular degeneration

MedlinePlus Genetics provides information about Age-related macular degeneration

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Dementia with Lewy bodies

The e4 version of the APOE gene can increase the risk of developing a form of dementia called dementia with Lewy bodies; however, some people with the APOE e4 allele never develop this condition. Dementia with Lewy bodies is characterized by intellectual decline; visual hallucinations; sudden changes in attention and mood; and movement problems characteristic of Parkinson's disease such as rigidity of limbs, tremors, and impaired balance and coordination.

People who inherit one copy of the APOE e4 allele have an increased chance of developing dementia with Lewy bodies. It is unclear how the APOE e4 allele contributes to the development of this condition. It is thought that the apolipoprotein E produced from the e4 allele of the APOE gene may disrupt the transport of a protein called alpha-synuclein into and out of cells. When alpha-synuclein is trapped inside or outside of cells, it accumulates in clusters, creating Lewy bodies. Accumulation of these clusters throughout the brain impairs neuron function and ultimately causes cell death. Over time, the loss of neurons increasingly impairs intellectual and motor function and the regulation of emotions, resulting in the signs and symptoms of dementia with Lewy bodies.

It is unclear why some people with the APOE e4 allele develop Alzheimer's disease while others develop dementia with Lewy bodies.

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Other disorders

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.

Other Names for This Gene

  • Apo-E
  • APOE_HUMAN
  • Apolipoproteins E

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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  • 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. doi: 10.1002/humu.20288. Citation on PubMed
  • 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. doi: 10.1002/em.20233. Citation on PubMed or Free article on PubMed Central
  • 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. doi: 10.1038/418932a. Erratum In: Nature 2002 Oct 3;419(6906):450. Citation on PubMed
  • Dickson DW, Heckman MG, Murray ME, Soto AI, Walton RL, Diehl NN, van Gerpen JA, Uitti RJ, Wszolek ZK, Ertekin-Taner N, Knopman DS, Petersen RC, Graff-Radford NR, Boeve BF, Bu G, Ferman TJ, Ross OA. APOE epsilon4 is associated with severity of Lewy body pathology independent of Alzheimer pathology. Neurology. 2018 Sep 18;91(12):e1182-e1195. doi: 10.1212/WNL.0000000000006212. Epub 2018 Aug 24. Citation on PubMed or Free article on PubMed Central
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  • Feussner G, Piesch S, Dobmeyer J, Fischer C. Genetics of type III hyperlipoproteinemia. Genet Epidemiol. 1997;14(3):283-97. doi: 10.1002/(SICI)1098-2272(1997)14:33.0.CO;2-6. Citation on PubMed
  • Heeren J, Beisiegel U, Grewal T. Apolipoprotein E recycling: implications for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):442-8. doi: 10.1161/01.ATV.0000201282.64751.47. Epub 2005 Dec 22. Citation on PubMed
  • 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. doi: 10.1016/j.exer.2006.08.001. Epub 2006 Sep 26. Citation on PubMed or Free article on PubMed Central
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  • 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. doi: 10.1073/pnas.0600549103. Epub 2006 Mar 27. Citation on PubMed or Free article on PubMed Central
  • 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. doi: 10.1016/j.neurobiolaging.2003.12.023. Citation on PubMed
  • 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. doi: 10.1016/s0361-9230(03)00067-4. Citation on PubMed
  • Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. doi: 10.1152/physrev.2001.81.2.741. Citation on PubMed
  • 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. doi: 10.7326/0003-4819-141-2-200407200-00013. Citation on PubMed
  • 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. doi: 10.1001/archopht.125.1.68. Citation on PubMed
  • 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. doi: 10.1212/01.wnl.0000228222.17111.2a. Citation on PubMed

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