Dementia-linked TDP-43 dysregulation in astrocytes impairs memory, antiviral signaling, and chemokine-mediated astrocytic-neuronal interactions.

Overall, our findings shed new light on TDP-43 dysregulation in astrocytes and its potential contributions to disease-related impairments in cognitive and immune-related functions. We report a novel chemokine-mediated astrocytic-neuronal pathway that is likely downstream of aberrant antiviral immune signaling in astrocytes that affects presynaptic release and neuronal activities. Together, these results implicate astrocytic TDP-43 dysregulation in the pathogenesis of dementia and point to chemokine signaling and CXCR3 as potential therapeutic targets for alleviating cognitive decline.