Sex differences in the association between apolipoprotein E ε4 allele and Alzheimer's disease markers

INTRODUCTION: We determined whether the effect of apolipoprotein E (APOE)-ε4 genotype on Alzheimer's disease (AD) markers differs in men and women across AD stages. METHODS: Among normal control (NC) participants (N = 702) and participants with mild cognitive impairment (N = 576) and AD (N = 305), we examined the associations of sex and APOE-ε4 carrier status with cortical amyloid-β (Aβ) burden, hippocampal volume ratio (HpVR; hippocampal volume/intracranial volume × 10(3)), brain glucose metabolism, and verbal memory. RESULTS: In NC, APOE-ε4 related to greater Aβ burden and poorer verbal memory across sex but to smaller HpVR and hypometabolism in men only. In mild cognitive impairment, APOE-ε4 related to smaller HpVR, hypometabolism, greater Aβ burden, and poorer verbal memory across sex. In AD, APOE-ε4 related to greater Aβ burden in men only and smaller HpVR across sex and showed no association with hypometabolism or verbal memory. DISCUSSION: Sex differences in the association between APOE-ε4 and AD markers vary by disease stage.