MAPT and neurodegenerative disease: Perhaps the strongest evidence of the involvement of frank lysosomal rupture in the pathogenesis of a neurodegenerative disease has been provided by the finding that lysosomal dysfunction is associated with AD and that lysosomal dysfunction is also associated with both the formation of β-amyloid peptide (Aβ) and the hyperphosphorylation of tau protein; two of the most important neuropathological features of AD are amyloid plaques and neurofibrillary tangles, which are caused by dysfunction and accumulation of Aβ and abnormally phosphorylated tau, respectively (review by reference [213]).