APOE

About APOE

APOE on chromosome 19q13.32 encodes apolipoprotein E, a major cholesterol carrier in the brain and a component of lipoproteins in the blood that mediates their uptake through LDL receptor family members. Three common alleles, E2, E3, and E4, differ at two amino acid positions and produce six genotypes. E3 is the most common allele. E4 is the strongest common genetic risk factor for late onset Alzheimer disease, with risk increasing further in people carrying two copies, although many E4 carriers never develop the disease. E4 may impair amyloid beta clearance and increase neuroinflammation, and E4 carriers are overrepresented among people with Alzheimer disease. E2 is associated with reduced Alzheimer risk. APOE also influences cardiovascular risk, as E4 is associated with higher LDL cholesterol and E2 with lower levels. Type III hyperlipoproteinemia, also called dysbetalipoproteinemia, occurs mainly in E2 homozygotes. The link between E4 and Alzheimer disease was reported by Allen Roses and colleagues in 1993. Because APOE genotype is a risk factor rather than a diagnosis, testing for Alzheimer risk is generally discussed in the context of genetic counseling.