MAPT and argyrophilic grain disease: More specifically, abnormal phosphorylation, aggregation, and proteolysis of the tau protein in a “pre-tangle” stage of neurofibrillary degeneration (Figure 4) has been neuropathologically documented to be an early and crucial event in the pathogenesis of AD, but also other sporadic tauopathies, such as AgD [131] and PSP.