APP and Alzheimer disease: Furthermore, this p25 was found to accumulate in brains of AD patients,67 suggesting that calpain‐cleaved p25 is at least in part responsible for the hyperphosphorylation of τ in the intracellular NFTs observed in AD brains.119 Moreover, the production of p25 resulted in an increased Aβ level in forebrain before any sign of neuropathology in APP transgenic mice75 probably through upregulation of BACE1 expression.68 Abnormal τ phosphorylation was observed in the APP/PS1120 and this was prevented by overexpressing CAST20 also suggesting calpain intervention.