Briefly, conservative speculation is that ApoE4 impedes mitophagy throughout protein synthesis and degradation, and there seems to exist a theoretical relationship between ApoE4, PINK1/Parkin-mediated mitophagy, and AD, which suggests an instructive hypothesis for neurodegenerative changes in AD involving various processes, including expression, cleavage, recruitment, ubiquitination, and degradation of PINK1 and Parkin at the molecular level. This evidence concerns the gene APOE and Alzheimer disease.