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.
The E4 seems to increase an individual's risk for developing type 2 Alzheimer disease, the late-onset form of this disorder. People who inherit one copy of the E4 allele have an increased chance of developing the disease; those who inherit two copies of allele are at even greater risk. E4 allele is associated with an increased number of protein clumps, called amyloid plaques, in the brain tissue of people with Alzheimer disease.
ApoE is also associated with cardiovascular disorders. People who carry at lease one copy of the E4 allele are at increased risk for 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.
People who carry two copies of the E2 allele are at risk for a condition known as hyperlipoproteinemia type III. This condition is characterized by increased levels of cholesterol, certain fats called triglycerides, and molecules called beta -VLDLs, which carry cholesterol and lipoproteins in the bloodstream.
E2 and E4 are both associated with higher plasma triglyceride concentrations. Over 90% of individuals with type III hyperlipoproteinemia are homozygous for the E2 allele. However, <10% of individuals homozygous for the E2 allele have overt type III hyperlipoproteinemia. This suggests that other genetic, hormonal, or environmental factors must contribute to the phenotypic expression of the disease. The E4 allele has been linked to pure elevations of low-density lipoproteins (LDL).