A comorbidity, characterized by massive increase in Αβ and murine tau hyperphosphorylation, is seen in a mouse model of hypersensitivity of astrocytes to Aβ, induced by inactivation of the protective stress response gene Sorcs2. Increased astrocyte distress coincides with a pro-inflammatory brain milieu and with prominent gliosis, further characteristics of human AD. The gene discussed is MAPT; the disease is Alzheimer disease.