Objective：To observe the neuroprotective effect of overexpression of neuroglobin（Ngb） on the cognitive function of Alzheimer’s disease（AD） double transgenic（APPswe/PS1dE9） mice，and to explore its mechanisms. Methods：The Ngb plasmid pNgb and empty vector pCDNA3.1 were successfully constructed and injected into the lateral ventricle of AD double transgenic（APPswe/PS1dE9） mice，which both led to overexpression of Ngb. Morris water maze was used to evaluate the effect of overexpression of Ngb on learning and memory ability and spatial exploration ability of AD mice；immunohistochemistry was used to detect the production of amyloid β-protein 42（Aβ42） in the brains；Caspase-3 and Caspase-9 activity detection kits were applied to detect Caspase-3/9 enzyme activity. Finally，the expression of p-Akt（ser473），total Akt and Caspase-3/9 in the brain tissues were detected by Western blot. Results：Overexpression of Ngb signif－icantly improved the learning and memory and spatial explo－ration ability of the AD mice（P<0.05），and reduced the activities of Caspase-3 and Caspase-9 and the generation of Aβ42 in the hippocampus（P<0.05）. Finally，Western blot results showed that overexpression of Ngb could inhibit the expression of Caspase-3 and Caspase-9 in the hippocampus of the AD mice（P<0.05），and also promote the phosphorylation of p-Akt（ser473）（P<0.05）. While，after the treatment of phosphatidylinositol-3 kinase（PI3K） inhibitor LY294002，the activities of Caspase-3 and Caspase-9 were evidently increased（P<0.05）. Conclusion：Overexpression of Ngb has a significant neuroprotective effect on the AD double transgenic（APPswe/PS1dE9） mice，and the mechanisms may be related to the reduction of generation of Aβ42，and the activation of PI3K/Akt signaling pathway，and then the inhibition of Caspase-dependent apoptosis pathway by Ngb.