MAPT and Alzheimer disease: The failure of proteolytic and autophagic mechanisms has been identified as one of the main reasons for the accumulation of tau26 and other protein aggregates, such as β-amyloid27 and amylin.28, 29, 30 In AD tau pathology, the reduced efficiency in the clearance of p-tau within autophagic vacuoles disrupts neuronal communication, leading to synaptic toxicity and, ultimately, cell death.31