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

Abstract 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 × 103), 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.