Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease.

Several studies have reported an association of the apolipoprotein E allele epsilon 4 (APOE4) to familial and sporadic late-onset Alzheimer's disease (LOAD). Here we report on the relationship between APOE4 and early-onset Alzheimer's disease (EOAD) in a Dutch population-based study. The frequency of the APOE4 allele was 2.3 times higher among EOAD cases compared to controls. Among patients, the allele frequency was 1.6 times higher in those with a positive family history than in those without. A significant increase in risk of EOAD was found for subjects homozygous for APOE4 regardless of family history of dementia, but an increase in EOAD risk for APOE4 heterozygotes could only be shown in subjects with a positive family history. Our study demonstrates a significant association between APOE4 and EOAD which is modified by family history of dementia.