BACE1 and Alzheimer disease: Upregulation of calpain activation in the brain of AD activates CDK5 through cleavage of p35 to p2567 and its homolog p39 to p2960 by excitotoxicity‐activated calpain and CDK5 activates BACE1 promoter by binding to its target STAT3, therefore increasing BACE1 expression, Aβ40 and Aβ42 production in transgenic mice.68 Thus, calpain overactivation leads to the two AD hallmarks, Aβ aggregates leading to SP and τ hyperphosphorylation leading to NFTs.