Sex Differences in Alzheimer’s Disease Pathogenesis

In recent years, the study of sex difference in Alzheimer’s disease (AD) has been a rapidly increasing topic of research. Men and women have distinct variances in terms of disease prevalence, risk factors, disease progression, biomarkers, and clinical and pathological presentation, according to research. Women are more likely than men to get AD, and their overall risk is higher. This gap may be explained in part by women’s greater life expectancy, as age is a prominent risk factor for AD. However, women’s greater life expectancy than males cannot fully explain the sex difference in AD. Women also experience more severe cognitive impairment and functional deterioration. These disparities could be attributed to variances in brain structure and biomarkers, sex hormones and chromosomes, genetic background (i.e., apolipoprotein E (APOE)), neuroinflammation, stress response, and other additional risk factors. This chapter summarizes the most recent research on sex differences in AD etiology, with an emphasis on the molecular mechanisms behind these disparities. A “precision medicine” strategy for AD that includes individualized, multimodal, and biomarker-driven and sex-sensitive prevention, diagnosis, drug discovery, and treatment plans will be made possible by elucidating sex variations in disease phenotypes.