Lastly, to elucidate the molecular mechanisms of APOE4‐induced mitochondrial impairment and synaptic degeneration in AD, we identified over 10 pivotal proteins (RASA2, BIG2, GPx‐1, MAP1LC3B, DNM1L, ATG9A, MAP1B, ANK‐2, PSD‐93, PKCγ, etc.)and several signaling pathways (Ras signaling pathway, PI3K‐AKT signaling pathway, Calcium signaling pathway, cAMP signaling pathway, Rap1 signaling pathway, etc.)that are significantly regulated by APOE4 and warrant further investigation. This evidence concerns the gene MAP1B and Alzheimer disease.