Apolipoprotein E, survival in Alzheimer's disease patients, and the competing risks of death and Alzheimer's disease

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Abstract
The apolipoprotein E (APOE) ε4 allele carries an increased risk of a patient developing Alzheimer9s disease (AD) while the ε2 allele carries a decreased risk. We compared survival from the onset of AD in subjects with different numbers of ε4 alleles and evaluated changes in genotypic frequencies with age. Two subject groups were investigated: unrelated AD case and control subjects, and affected and unaffected members from 74 multiplex AD families. In both subject groups, survival from onset decreased with increasing onset age, was longer in women, and was unrelated to ε4 gene dose. The ε2/ε3 genotype became more common with age (p = 0.004). The ε4 allele decreased in frequency with age in all patient groups but, unexpectedly, remained unchanged in control subjects. We conclude that the progression of AD is not strongly related to ε4 gene dose, that the higher prevalence of AD in women may involve the longer survival of affected women, and that AD and death are competing risks involving APOE that change over time.

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