Abstract: Objective To study the association between leptin and Alzheimer's disease (AD). Methods SH-SY5Y cells were randomly divided into control group, Okadaic acid (OA) injury model group, and leptin treatment group.An AD model was established by inducing SH-SY5Y with 40nmol/L OA.Leptin treatment group was treated with 0.4μg/ml exogenous leptin for 6 h.Expression levels of cell cycle-dependent Cdk5 and β-actin proteins were measured by Western blot.ObR and Cdk5 colocalization was detected by dual immunof luorescent staining assay. Results Western blot showed that the Cdk5 expression level was signif icantly higher after the model was established (P< 0.01) and significantly lower after leptin was given (P< 0.01).Double immunofluorescence staining assay showed that the ObR and Cdk5 proteins were expressed mainly in cytoplasm of SH-SY5Y cells.The red and green markers were overlapped into orange fluorescence, which could be considered as the co-localization of the two proteins, suggesting that ObR interacts with Cdk5. Conclusion Leptin can down-regulate Alzheimer's disease-related Cdk5 expression in vitro, thus providing a new target for the treatment of Alzheimer's disease.