MAPT and tauopathy: There are three major findings in this study; MW181 can reduce inflammation-induced p38α MAPK activation and tau phosphorylation in primary neurons in vitro; MW181 can block tau phosphorylation and aggregation in a 20-month-old hTau mouse model of tauopathy with an advanced stage of tau pathology; and evidence consistent with a p38 MAPK-mediated pathway playing an important role in tau pathology was provided by the resistance of MK2–/– mice to inflammation-induced tau hyperphosphorylation.