Alzheimer disease(AD)is the leading cause of age-related dementia,gradually destroys patient's learning and memory,and involves loss of basal forebrain cholinergic neurons.Neural stem cells(NSCs)transplatation thearpy aims to supply the loss of cholinergic neurons and restore the function of the damaged nervous system.The purpose of this study was to evaluate the therapeutic effects of combined NGF-PEG-PLGA-NPs and neural stem cells transplanting into 192 IgG-Saporin rat model of AD.NSCs were induced by using the same concentration of NGF and NGF-PEG-PLGA-NPs in vitro.β-Tubulin Ⅲ labeling immunofluorescence was used to detect the neuron differentiation of NSCs.It was showed that there were no statistical differences between control group and BSA-PEG-PLGA-NPs group(P>0.05),either between 50ng/mlNGF group and NGF-PEG-PLGA-NPs group(P>0.05),But the ratios of neural differentiation in 50ng/mlNGF group and NGF-PEG-PLGA-NPs group were both higher than other two groups(P<0.05).In vivo,NGF-PEG-PLGA-NPs and NSCs were cambained and transplated into basal forebrain and hippocampal areas of AD rats.Learning and memory abilities were tested by Morris water maze,basal forebrain cholinergic neurons and hippocampal synaptophysin changes were detected by Immunohistochemistry,and hippocampus AchE fibers changes were detected by histochemistry staining.The results of Morris water maze showed that the escape time in NSC transplantation group,combined NGF-PEG-PLGA-NPs and NSC transplantation group was all shorter than that in AD modal group(P<0.05),And the time of across platform,the swimming time in platform quadrant were all more than that in modal group(P<0.05).Furthermore,the swimming distance in platform quadrant in combined NGF-PEG-PLGA-NPs and NSC transplantation group was more than that in NSC transplantation group(P<0.05).the numbers of basal forebrain cholinergic neurons in combined NGF-PEG-PLGA-NPs and NSC transplantation group was more than that in NSC transplantation group(P<0.05).Immunohistochemistry detection showed that the numbers of basal forebrain cholinergic neurons and synaptophysin staining average absorbance values in combined NGF-PEG-PLGA-NPs and NSC transplantation group were more than that in NSC transplantation group(P<0.05).Histochemistry staining detection showed that AchE positive fibers in combined NGF-PEG-PLGA-NPs and NSC transplantation group were more than that in NSC transplantation group(P<0.05).The results indicate that NGF-PEG-PLGA-NPs promoted NSCs neural differentiation,and the effect was quite the same concentration of NGF in vitro.NSCs transplantation therapy and combined NGF-PEG-PLGA-NPs and NSCs transplantation therapy both improved learning and memory abilities of AD rats,and had supplementary effects on p75-positive cholinergic neurons in basal forebrain and promoted the formation of synapses and regeneration of AchE positive fibers in hippocampus.Combined NGF-PEG-PLGA-NPs and NSCs transplantation therapy was more effective than NSC stransplantation therapy for AD modal rats.