MAPT and Alzheimer disease: Evidence also revealed that enhanced intracellular Ca2+ due to Aβ induced mitochondrial dysfunction and ER stress activates caplapin dependent cleavage of P35 and P39 generating P25 and P29 fragments, which in turn activates Cdk5 followed by activation of GSK3β leading to hyperphosphorylation of tau protein forming NFT in AD brain as observed in transgenic animals [94,95].