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. The gene discussed is DLG2; the disease is Alzheimer disease.