APOE and Alzheimer disease: Possession of the APOE-ɛ4 allele has become firmly established as a risk factor for the incidence of late-onset AD (LOAD).63 The frequency of the ɛ4 allele in familial LOAD was found to be 50% compared with 14–16% for controls64 and 40% in those with autopsy-confirmed AD pathology but no family history.65 AD risk and APOE-ɛ4 carriage is dose dependent: individuals who are heterozygous and homozygous for APOE-ɛ4, have a threefold and eightfold increased risk of developing LOAD by age 80 years, respectively.