MAPT and Alzheimer disease: Notably, aside from the build-up of neurofibrillary tangles (NFTs) as a key neuropathological feature of AD and other tauopathies, pathological Tau is also highly concentrated at synapses and plays a central role in perturbing synaptic function [142-152], suggesting a critical role of autophagy failure in the build-up of Tau and Tau-mediated toxicity.