APOE and Alzheimer disease: Looking at the above factors, it is supposed that the ApoE-VDAC binding cooperates with the VDAC1-Aβ and VDAC1-Tau interaction conjointly blocks mitochondrial pores as synergistic effects, ultimately contributing to mitochondrial dysfunction, defective mitophagy, and aberrant accumulation of damaged mitochondria, interrupting energy supply and aggravating synaptic dysfunction in AD.