MAPT and Alzheimer disease: In fact, AD is histopathologically defined by the presence of amyloid-beta plaques and tau-related neurofibrillary tangles, which have been associated with local synaptic disruptions, loss of fibers and neuronal death: this evidence suggests that AD is a dysconnectivity disease [7,8,9,10,11,12] whose early stages are due to synaptic failure.