KDM6A expression is associated with a sex‐disease interaction in activated microglia

There is increasing evidence indicating sex‐specific patterns in disease manifestation and sex differences in the rates of cognitive decline and brain atrophy. Women are protected, relative to men, at the prodromal phases but later exhibit steeper cognitive decline and higher brain atrophy rates1. Sex‐related differences in AD‐associated genes are starting to emerge. The X‐linked gene, KDM6A, avoids X‐inactivation and the resulting elevation in expression confers resilience in women2. KDM6A is also dysregulated in disease associated microglia (DAM) in the 5XFAD mouse model3. We sought to identify if activated microglia was the effector cell type for the KDM6A resilience effect in the brain using single‐nucleus RNA‐seq (snRNA‐seq).