Seven proteins, GPx‐1 (Gpx1), MAP1LC3B (Map1lc3b), DNM1L (Dnm1l), ATG9A (Atg9a), MAP1B (Map1b), ANK‐2 (Ank2) and PSD‐93 (Dlg2) were positioned as the key nodes of the “bridge” Additionally, ANK‐2 (Ank2) and PKCγ (Prkcg), which are both mitochondrial and synaptic proteins, occupied pivotal positions in the synaptic protein network and may be involved in mitochondrial dysfunction‐mediated synaptic degeneration in E4‐AD mice. Here, ANK2 is linked to Alzheimer disease.