Apolipoprotein E gene in physiological and pathological aging

Introduction: The genetic background plays a role on longevity. The distribution of the apolipoprotein E gene (APOE) variants (ε2, ε3, ε4) may differ across age groups, especially in the oldest old and despite geographical and ethnic specificities. Since the ε4 variant is associated with Alzheimer's disease (AD), it might represent an opportunity for exploring the relationship of APOE with physiological and pathological aging. Aim: To explore the role played by APOE genotype/alleles on physiological and pathological brain aging. Materials and Methods: The study was conducted in a cohort of centenarians (n = 106), and two cohorts of octogenarians (without cognitive decline, n = 351 controls; and with AD, n = 294). Results: No significant differences in genotype/allele distributions were observed comparing controls to centenarians. The prevalence of ε2/ε3, ε3/ε3, ε3/ε4 and ε4/ε4 genotypes were significantly different in centenarians compared to AD. The prevalence of ε2 and ε3 alleles were significantly higher in centenarians, whereas the ε4 was less frequent. The ε4 allele was positively associated with AD, whereas a negative association was found for ε2 and ε3 alleles. Conclusions: Our study indicates that ε4 allele is strongly associated with AD. APOE significantly affects AD risk, but apparently not longevity.