Sex‐dependent molecular landscape of Alzheimer's disease revealed by large‐scale single‐cell transcriptomics

Single-cell transcriptomics reveals significant sex-specific molecular signatures in Alzheimer's disease (AD). Male astrocytes show enhanced modulation of apoptotic and cell death pathways in AD; female astrocytes exhibit distinct alterations in Wnt signaling and cell-cycle regulation. Sex-dimorphic changes in mitochondrial gene expression are observed in excitatory neurons, suggesting divergent energy metabolism profiles may contribute to AD sex differences. RPTOR is identified as a key regulator of male-specific changes in astrocytes, implicating the mechanistic target of rapamycin pathway in sex-dependent AD pathology. New cell-cell communication analyses reveal sex-specific patterns of intercellular signaling, providing insights into how cellular interactions may differentially contribute to AD pathology in males and females.