Apolipoprotein E gene in physiological and pathological aging

Abstract Introduction The genetic background plays a role on longevity. The distribution of the apolipoprotein E gene ( APOE ) variants (e2, e3, e4) may differ across age groups, especially in the oldest old and despite geographical and ethnic specificities. Since the e4 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 e2/e3, e3/e3, e3/e4 and e4/e4 genotypes were significantly different in centenarians compared to AD. The prevalence of e2 and e3 alleles were significantly higher in centenarians, whereas the e4 was less frequent. The e4 allele was positively associated with AD, whereas a negative association was found for e2 and e3 alleles. Conclusions Our study indicates that e4 allele is strongly associated with AD. APOE significantly affects AD risk, but apparently not longevity.