Objective: To investigate the protection of Compound JSW prescription on nerve injury of in the hippocampal area the APPV717 I transgenic mice. Methods: Three-month-old APPV717 I transgenic mice (30) were randomly divided into three groups by ig administration of Compound JSW prescription at doses of 0.075, 0.15, or 0.3 g/kg/d, a group by ig administration of Donepezil at dose of 0.92 mg/kg/d, an APPV717 I transgenic model group, and a normal group by ig administration of distilled water. APPV717 I transgenic mice were administered with Compound JSW prescription for eight months. The spatial memory ability was measured in Morris water maze. The nerve injury in the hippocampal CA1 region was observed by electronic microscopy. The number of Shank1 positive cells, total area covered by Shank1, and integral optiCal density in CA1 subfield within the hippocampus were determined using immunohistochemical stains and Image-Pro plus analysis. Results: After eight-month treatment with Compound JSW prescription, the mean escape latency period was significantly shortened (P<0.05), and the target quadrant swimming time was significantly lengthened (P<0.05 and 0.01) compared to the APPV717 I transgenic model mice. The ultrastructure of hippocampal CA1 region showed Compound JSW prescription ameliorated the denaturation and necrosis of neurons and increased the amount of nerve synapse with integral structure. Furthermore, the number of Shank1 positive cells, total area cover by Shank1 and their integral optical density in the hippocampal CA1 area of the APPV717 I transgenic mice treated with Compound JSW prescription were significantly increased more than those of the APPV717 I transgenic model mice (P<0.05 and 0.01). Conclusion: Compound JSW prescription could ameliorate the nerve injury and increase the expression of Shank1 in CA1 subfield within hippocampus, and this might lead to the development of novel treatment for the memory loss of APPV717 I transgenic mice suffered from Alzheimer's disease.