Microglial microRNAs mediate sex-specific responses to tau pathology

Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by microRNAs, but it is unknown whether microglial microRNAs have sex-specific influences on disease. We show in mice that microglial microRNA expression differs in males and females and that loss of microRNAs leads to sex-specific changes in the microglial transcriptome and tau pathology. These findings suggest that microglial microRNAs influence tau pathogenesis in a sex-specific manner. Kodama et al. show that microglia from male and female adult mice have distinct microRNA profiles and that loss of microglial microRNAs leads to sex-specific changes in the microglial transcriptome and tau pathology.