MAPT and Alzheimer disease: 5). Only 5% of AD is familial and results from mutations in presenilin 1, presenilin 2, and amyloid precursor protein (APP). Aβ and tau protein are substrates for autophagy. An abundance of autophagic structures containing these substrates is observed in AD. In addition, it has been shown that abnormal conformations of Aβ reduce lysosomal amplification, lead to synaptic defects and increase the course of the disease (Ref. 85).