MAPT and Alzheimer disease: It is known that insoluble tau present in AD brain is phosphorylated at more than 45 residues by various kinases, including glycogen synthase kinase-3 (GSK-3), cyclin-dependent kinase-5 (cdk5), casein kinase 1 (CK1), and cyclic AMP-dependent protein kinase (PKA), while it is dephosphorylated by phosphatases such as PP2A [319].