Apolipoprotein E ϵ4/4 in a Neuropathologically Normal Very Elderly Individual

A strong genetic disequilibrium has recently been found between the ϵ4 allele of the apolipoprotein E (ApoE) gene and the development of Alzheimer's disease (AD). 1 Corder and colleagues 2 surmised that inheritance of two ApoE ϵ4 alleles was "virtually sufficient to cause AD by age 80 [years]" in their group of late-onset familial patients with AD. To test the hypothesis that homozygosity for ApoE ϵ4 is associated with nearly inevitable development of AD in elderly individuals, we used a polymerase chain reaction—based restriction enzyme technique 3 to evaluate the genotypes of very elderly individuals who, by neuropathological examination of the brain, did not have AD. Of six control subjects older than 80 years (mean±SD, 87.2±8.1 years), one was found to be genotypically ApoE ϵ4/4. This was an 86-year-old man with no history of neurological disease. Sections from multiple cortical areas stained with Bielschowsky's silver method and with thioflavine S