MAPT and Alzheimer disease: It seems likely that synpatosomal calpain-2 hyperactivation which is observed as a consequence of elevated β-amyloid (Fig. 6) occurs early in AD pathogenesis43 and calpain-1 hyperactivation which occurs later in the disease progression is the main contributor to tau pathology in AD via the GSK 3β-PP2A pathway47 and dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk 1A48) pathways.