The apolipoprotein E epsilon 2 allele is associated with an increased risk of early-onset Alzheimer's disease and a reduced survival.

It was suggested that in contrast to the E4 allele, the E2 allele of the apolipoprotein E gene (APOE2) has a protective effect for late-onset Alzheimer's disease and early-onset Alzheimer's disease (EOAD). We studied the role of the APOE2 allele in the pathogenesis of EOAD in a Dutch population-based study of 175 probable EOAD patients with onset age at or before 65 years and 532 age-matched controls. In our population, there was no evidence for a protective effect of the APOE2 allele on the risk of EOAD. However, our data show that among EOAD patients, survival for APOE2 carriers was significantly reduced. When restricting the analysis to patients ascertained early after diagnosis at a stage of disease when mortality is low, our data suggest an increased risk of EOAD for subjects with APOE2E2, APOE2E3, APOE3E4, and APOE4E4 genotypes.