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 colleagues2 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 technique3 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
Hyman BT, Hedley-Whyte ET, Rebeck GW, Vonsattel J, West HL, Growdon JH. Apolipoprotein E ϵ4/4 in a Neuropathologically Normal Very Elderly Individual. Arch Neurol. 1996;53(3):215. doi:10.1001/archneur.1996.00550030017010
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