Apolipoprotein E (ApoE) plays an important role in the catabolism of lipoproteins and cholesterol.
Three major alleles of ApoE are known; E2 (Cys112/Cys158) (, E3 (Wild-type; Cys112/Arg158) and E4 (Arg158/Arg158.
A meta-analysis of clinical and autopsy-based studies demonstrated that, in white individuals, risk of AD was
increased in individuals with one copy of the ε4 allele (E2/E4, OR 2.6; E3/E4, OR 3.2) or two copies (E4/E4, OR 14.9)
compared with those with an E3/E3 genotype (Wild-type).
Conversely, the E2 allele of APOE has a protective effect against AD: the risk of AD in individuals carrying
APOE E2/E2 (OR 0.6) or E2/E3 (OR 0.6) is lower than in those carrying E3/E3 (Wild-type).
APOE E4–AD association was weaker among African American (E4/E4, OR 5.7) and Hispanic (E4/E4, OR 2.2)
populations, and was stronger in Japanese people (E4/E4, OR 33.1) compared with white individuals (E4/E4, OR 12.5).
APOE E4 is associated with increased prevalence of AD and lower age of onset. The frequency of AD and mean age
at clinicalonset are 91% and 68 years in E4 homozygotes, 47% and 76 years in E4 heterozygotes, and 20% and 84 years in E4
noncarriers indicating that APOE E4 confers dramatically increased risk of development of AD with an earlier
age of onset in a gene dose-dependent manner.