【Abstract】 Objective To explore the neuroprotective effect of brain-targeted peptide modified BDNF on Alzheimer 's disease mice. Methods A brain-targeted peptide (TGN) was linked to BDNF by genetic engineering. The recombinant protein (TGN-BDNF) was expressed, and then the recombinant protein was identified by polyacrylamide gel electrophoresis (SDS-PAGE) and western blot (WB). The recombinant protein was intraperitoneally injected into APP/PS1 double transgenic mice, and the content of BDNF in brain tissue was detected by enzyme-linked immunosorbent assay (Elisa). The experiment was divided into control group, model group, BDNF group and TGN-BDNF group. Morris water maze test was used to measure the spatial learning and memory ability. Elisa was used to detect the content of Ap ? Tau protein and acetylcholine in hippocampus. WB was used to detect the expression of TrkB/Erk/CREB signaling pathway. Results The molecular weights of BDNF and TGN-BDNF were 15. 79kd and 17. lOkd respectively, which were confirmed by SDS- PAGE and WB. Compared with model group and BDNF group, the content of BDNF in brain tissue of TGN-BDNF group increased at 30 min, 1 h and 3 h after injection (P<0.05) , but there was no significant difference at 6 h after injection (P〉0.05). Compared with model group and BDNF group, the latency in the 5th day of TGN-BDNF group decreased, and the number of stage-crossing increased (P<0.05) ； the content of Ap and Tau protein in the hippocampus decreased, the content of acetylcholine increased (P<0.05) ； the expression of p-TrkB, p-Erk and p-CREB increased (P<0.05). Conclusion Brain-targeted peptide modified BDNF has a good brain-targeted ability. It can improve the spatial learning and memory ability of mice with Alzheimer's disease, reduce the content of Ap and Tau protein in hippocampus, increase the content of acetylcholine, promote the activation of TrkB/Erk/CREB signaling pathway, which provide a new idea for the treatment of Alzheimer's disease.