Although abnormal hyperphosphorylation and Tau aggregation make it resistant to proteolysis by calcium-activated neutral proteases [46], there are also data suggesting that calpain-mediated Tau cleavage precedes Tau phosphorylation in Aβ-treated hippocampal neurons, suggesting that it might be an early event in the pathological process shared by multiple tauopathies. This evidence concerns the gene MAPT and tauopathy.