CDK5 and Alzheimer disease: During Aβ production, GSK3β promotes the phosphorylation of APP and aggravates the β-cleavage of APP,206,207 and also inhibits APP autophagic degradation by reducing lysosomal biogenesis, thereby increasing Aβ levels in AD animal and cell models.105 In NFT formation, GSK3β acts as one of the major tau kinases by specifically phosphorylating tau at Thr231, which accelerates tau dissociation from the microtubules, promoting tau oligomerization and NFT formation.208 GSK3β interacts with other kinases such as CDK5 to amplify the hyperphosphorylation of tau.