In conclusion, our study not only places ‘early’ Tau pathology (pTau) upstream of microglial NLRP3 inflammasome activation in Tauopathies, but also highlights the role of Tau as an acetyltransferase in NLRP3 acetylation and provides new insight into the potential early diagnostic marker and therapeutic target for AD and related Tauopathies. Here, MAPT is linked to Alzheimer disease.