Apolipoprotein E (apoE) was discovered as a plasma protein involved in lipoprotein metabolism. ApoE is synthesized by the liver and is also made locally in the brain. There are three common variants of apoE, resulting from common genetic variation, called E2, E3 and E4. The E3 allele is the most prevalent form, and the proportion of the three alleles differs between populations. Epidemiological studies have found that the E4 allele is associated with decreased longevity, increased plasma cholesterol levels and increased prevalence for cardiovascular disease and particularly for Alzheimer's disease. The apoE polymorphism also affects response to head trauma, cognitive decline upon ageing and several other disorders. Thus, common genetic variation in the apoE gene may be associated with successful ageing.