Exploring Proteomic Differences in PBMCs for Sex-Specific Insights into Alzheimer's Disease.

Peripheral blood mononuclear cells (PBMCs) offer a minimally invasive window into systemic biology and immune dysregulation in Alzheimer's disease (AD). We performed quantitative proteomic profiling of PBMCs from male and female AD patients and controls to assess sex differences. AD was associated with proteomic remodeling, with complement activation, coagulation, and neuronal signaling enriched in males, whereas females showed increased steroid hormone secretion, lipid metabolism, and acute-phase response with reduced translation and DNA maintenance. Despite distinct patterns, both sexes exhibited immune and hemostatic activation, underscoring shared systemic mechanisms and the need for sex-specific biomarkers and therapeutic strategies in AD.