MAPT and Alzheimer disease: PP2A has a leading role in AD, which has been well reviewed elsewhere.140,141 Tau is phosphorylated as a result of the crosstalk between protein kinases, such as glycogen synthase kinase-3β (GSK3β), CDK, and ERK, and phosphatases, including PP2A.142–145 Mechanistically, PP2A is inactive in the nucleus and active in the cytoplasm, thereby preventing the hyperphosphorylation of cytoplasmic tau.