Second, the abnormal interactions between DRP1 and hyperphosphorylated Tau, as well as DRP1 and Aβ monomers and oligomers, are established by coimmunoprecipitation (co-IP) and double-labeling immunofluorescence analysis, in postmortem brain tissues of AD patients and brain homogenates from several AD mouse models (Manczak et al., 2011; Reddy et al., 2011; Manczak and Reddy, 2012a; Abtahi et al., 2020; Kandimalla et al., 2021), which is speculated that excessive p-Tau and Aβ accumulation may synergistically disrupt mitochondrial fragmentation in a ApoE4-dose-dependent manner. This evidence concerns the gene APOE and Alzheimer disease.