MAPT and Alzheimer disease: These disruptions interfere with clearance mechanisms involving substrate engulfment, autophagosome formation, autophagosome-lysosome fusion, and lysosomal structure and function.227,229 In AD, autophagy defects mediate the disruption of protein homeostasis networks (production and extracellular secretion of Aβ, abnormal aggregation of tau protein) and lead to the accumulation of damaged organelles, such as dysfunctional mitochondria.231 In summary, abnormalities of autophagy are intimately related to the onset and progression of AD.