We have summarized ApoE4 regulation on the stages shared by mitophagy and autophagy and illustrated the insights underlying AD-targeted therapy, then we will discuss the association between ApoE4 and mitophagy from the perspective of mitophagy-exclusive processes, including mitochondrial dynamic equilibrium (fission and fusion), and mitophagy-specific induction. This evidence concerns the gene APOE and Alzheimer disease.