Role of the gut microbiome in mediating sex-specific differences in the pathophysiology of Alzheimer's disease.

ABSTRACT

Alzheimer's disease (AD) presents distinct pathophysiological features influenced by biological sex, with women disproportionately affected due to sex-specific genetic, hormonal, and epigenetic factors. This review delves into three critical areas of sex differences in AD First, we explore how genetic predisposition and hormonal changes, particularly those involving sex-specific modifications, influence susceptibility and progression of the disease. Second, we examine the neuroimmune dynamics in AD, emphasizing variations in microglial activity between sexes during crucial developmental stages and the effects of hormonal interventions on disease outcomes. Crucially, this review highlights the significant role of gut microbiome perturbations in shaping AD pathophysiology in a sex-specific manner, suggesting that these alterations can further influence microglial activity and overall disease trajectory. Third, we provide a viewpoint that advocates for personalized therapeutic strategies that integrate the understanding of hormonal fluctuations and microbiome dynamics into treatment plans in order to optimize patient outcomes.