APOE
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Definition: APOE is a lipoprotein involved in lipid trafficking between neurons and astrocytes.
Apolipoprotein E (ApoE) is the major apolipoprotein of the CNS that has a central role in cholesterol transport. In the brain, ApoE is mostly produced by astrocytes, and some binds to specific neuronal receptors for cholesterol uptake. However, neurons also synthesize ApoE.
Amino acid substitutions at positions 112 and 158 define three isoforms in the human population. Isoform 4 (ApoE4) is significantly associated with sporadic Alzheimer disease, whereas isoform 2 might protect against Alzheimer disease (AD).
One allele (ε4) of the apolipoprotein E (ApoE) gene on chromosome 19 increases the risk of Alzheimer disease and lowers the age at onset of the disease.
Individuals with the ε4 allele are overrepresented in populations of patients with Alzheimer disease compared with control populations, and their Aβ burden in the brain is larger.
ApoE can bind Aβ and is present in plaques, but how this allele increases the risk for Alzheimer disease has not been established.
Pathology
APOE4 isoform in Alzheimer disease
APOE in prostatic carcinoma
longevity
- Common polymorphisms of APOE have a slight effect on lifespan.
Alzheimer disease
In families with late-onset AD, the risk for AD increased from 20% to 90% and mean age of onset decreased from 84 to 68 years with increasing number of apolipoprotein E epsilon 4 (APOE4) alleles.
Overall homozygozity for APOE4 increases the relative risk by 15- to 18-fold. This makes APOE the most effective risk factor for AD aside from age.
References
Adalbert R, Gilley J, Coleman MP. Abeta, tau and ApoE4 in Alzheimer’s disease: the axonal connection. Trends Mol Med. 2007 Apr;13(4):135-42. PMID: #17344096#
Christensen K, Johnson TE, Vaupel JW. The quest for genetic determinants of human longevity: challenges and insights. Nat Rev Genet. 2006 Jun;7(6):436-48. PMID: #16708071#
Poirier J. Apolipoprotein E and cholesterol metabolism in the pathogenesis and treatment of Alzheimer’s disease. Trends Mol Med. 2003 Mar;9(3):94-101. PMID: #12657430#
Herz J, Beffert U. Apolipoprotein E receptors: linking brain development and Alzheimer’s disease. Nat Rev Neurosci. 2000 Oct;1(1):51-8. PMID: #11252768#