Alzheimer's disease (AD) exhibits sex-dependent differences in risk, progression, and pathology. This review explores the biological mechanisms underlying these differences, including sex hormones, sex chromosomes, and sex-specific gene expression. The review highlights the role of estrogen in protecting against AD, the impact of sex chromosomes on gene expression, and the influence of sex on autophagy, metabolism, and the gut microbiome. It also discusses the importance of considering sex in clinical trials and genetic studies to improve understanding and treatment of AD. The review emphasizes the need for sex-stratified research to address the disparities in AD risk and progression between men and women. Additionally, it notes the challenges in studying sex differences due to methodological limitations, such as the exclusion of female subjects in many studies and the lack of appropriate statistical tools for analyzing sex-linked genetic associations. The review concludes that understanding sex differences in AD is crucial for developing more effective and personalized treatments for both men and women.Alzheimer's disease (AD) exhibits sex-dependent differences in risk, progression, and pathology. This review explores the biological mechanisms underlying these differences, including sex hormones, sex chromosomes, and sex-specific gene expression. The review highlights the role of estrogen in protecting against AD, the impact of sex chromosomes on gene expression, and the influence of sex on autophagy, metabolism, and the gut microbiome. It also discusses the importance of considering sex in clinical trials and genetic studies to improve understanding and treatment of AD. The review emphasizes the need for sex-stratified research to address the disparities in AD risk and progression between men and women. Additionally, it notes the challenges in studying sex differences due to methodological limitations, such as the exclusion of female subjects in many studies and the lack of appropriate statistical tools for analyzing sex-linked genetic associations. The review concludes that understanding sex differences in AD is crucial for developing more effective and personalized treatments for both men and women.