Several previous studies reported that Cdk5 activator p35 was cleaved into p25 in a calpain-dependent manner, resulting in elevated Cdk5 activation and tau hyper-phosphorylation in AD patient brains and mouse models of AD when the intracellular calcium concentration was abnormally high (Kusakawa et al., 2000; Lee et al., 2000). This evidence concerns the gene MAPT and Alzheimer disease.