MAPT and Alzheimer disease: GSK-3β (Glycogen synthase kinase-3β) is considered to be the most important protein kinase regulating Tau phosphorylation [52], GSK-3β has been shown to be highly associated with Aβ and Tau in the pathogenesis of AD [53], In Tet/GSK-3β mice with AD pathological features, restoration of normal GSK-3β activity after transgene shutdown resulted in normalized Tau phosphorylation levels, reduced neuronal death and reactive glial cell response, and improved cognitive deficits [54].