MAPT and Alzheimer disease: Studies conducted in neuronal cultures using exogenous applications of pathological Aβ show that this treatment can directly induce tau hyperphosphorylation and cause neuritic degeneration [113], and it has also been shown in mouse models of AD that the presence of tau is necessary for canonical Aβ-induced disease phenotypes such as loss of LTP [58] and cognitive decline [57] to develop.