APOE ‐associated disease risk and sex‐specific effects in Egyptian Alzheimer's disease: an exploratory study

Abstract INTRODUCTION The apolipoprotein E ( APOE ) gene is the strongest known genetic risk factor for late‐onset Alzheimer's disease (AD), particularly the ε4 allele. Evidence suggests that women carrying at least one APOE ε4 allele have a higher risk of developing AD compared to men. However, data addressing genetic risk and sex‐specific effects in Middle Eastern and North African populations remain limited. METHODS To address this gap, we evaluated APOE allele frequencies, their association with AD risk, and their contribution to sex‐specific variability in a cohort of 63 clinically diagnosed AD patients and 201 cognitively healthy controls recruited across Egypt. RESULTS The APOE ε3 allele was the most prevalent in both AD cases (83.3%) and controls (83.6%). The ε4 allele was more frequent among AD patients (12.7%) than controls (8.0%) (adjusted odds ratio OR = 1.09, 95% confidence interval CI: 0.46 to 2.49, p = 0.85), while the ε2 allele was less frequent in AD patients (4.0%) compared to controls (8.5%) (adjusted OR = 0.82, 95% CI: 0.24 to 2.36, p = 0.73). However, neither association reached statistical significance after Benjamini–Hochberg false discovery rate correction. Sex‐stratified analyses revealed no significant sex‐specific effects of APOE alleles. CONCLUSION This pilot study provides the first characterization of APOE genotype and allele frequencies in Egyptians with clinically confirmed AD. No statistically significant association was observed between APOE status and AD risk in either males or females. Larger, geographically representative studies are needed to further elucidate the role of APOE in AD susceptibility within the Egyptian population and to explore potential alternative genetic or environmental contributors.