MAPT and Alzheimer disease: GSK3 is modulated through a variety of pathways including wnt, phosphatidylinositide-3 kinase (PI3K) and Akt deactivate GSK-3β by phosphorylating Ser9 [58, 59], increasing GSK-3β, in pre-tangles which is closely associated with tangle-bearing neurons suggesting a role in tau hyperphosphorylation in AD [60–64].