Gender and age modify the association between APOE and AD-related neuropathology

Objective: To assess the impact of apolipoprotein E (APOE) polymorphism on AD-related neurofibrillary tangle (NFT) formation and senile plaques (SP). Methods: A sample of 729 routine autopsy brains (359 men, 370 women; age range, 60 to 99 years) was investigated. All brains were classified neuropathologically according to a procedure permitting differentiation of six NFT stages and three SP stages. APOE genotyping was performed on all cases. Results: The epsilon4 allele of APOE was associated not only with SP (p < 0.0001) but also with NFT formation (p < 0.0001). The effect of the epsilon4 allele on NFT formation was noted at ages greater than or equal to 80 years (p < 0.0001) but not between ages 60 and 79 years (p = 0.12). An association between the <epsilon>4 allele and SP for women was found at ages 60 to 79 years (p < 0.0001) but not at <greater than or equal to>80 years of age (p = 0.063). By comparison, men showed an association in both age categories (p = 0.001 and p = 0.001). Conclusion: The results confirm the association between the epsilon4 allele and both typos of AD-related lesions and show that this association is differentially modified by age and gender.