MAPT and Alzheimer disease: p35 is a regulatory protein that activates CDK5, and calpain-catalyzed cleavage of p35 in response to elevated cytosolic Ca2+ that occurs in neurons during the pathogenesis of AD cleaves p35 to form p25, which hyperactivates CDK5 and causes increased tau phosphorylation (Kimura et al., 2014; Seo et al., 2017).