MAPT and tauopathy: In the present study, we find that LM11A-31 diminishes upstream signaling relevant to tau modification, including calpain and tau kinase activities, and mitigates disease correlates and outcomes in these mice including accumulation of human pathological tau species, tau seeding activity, synaptic degeneration, microglial activation, behavioral impairment and early death in PS19 (P301S) tauopathy mice.