Taken together, the upregulation of astrocytic Piezo1 that we see around amyloid plaques in the hippocampus and cortex of TgF344-AD rats could, on the one hand, contribute to AD-associated astrogliopathy and neurodegeneration but, on the contrary, astrocytic Piezo1 may instead drive anti-inflammatory signaling cascades through YAP-mediated suppression of cytokine signaling that work in concert to reduce reactive astrogliosis and neuroinflammation in the aging AD brain. Here, PIEZO1 is linked to Alzheimer disease.