Objective:Synaptic loss in the hippocampus in Alzheimer's disease (AD) has been shown to be closely associated with the cognitive impairment.Synaptic dysfunction is a pathological feature that occurs prior to synaptic loss and mainly depends on structural changes and alterations of synaptic proteins.Evidence has suggested that curcumin,obtained from the traditional Chinese medicine—Turmeric (Curcuma longa L.),can ameliorate cognitive impairment,but few studies have focused on the mechanism by which curcumin affects synapses at early stages of AD.Therefore,we performed a study to investigate whether curcumin exerted its effect on synapses at the early stage in AD.Methods:We used 3-month-old APPswe/PS1dE9 mice and wild type (WT) littermates of the APPswe/PS1dE9 mice from the same colony as the normal controls.Seventy-five APPswe/ PS1dE9 mice were allocated to the Model group,Rosiglitazone group,and Curcumin groups randomly.The Wild and Model groups were orally administered an equal amount of 0.5% carboxymethyl cellulose (CMC).We observed the ultrastructure of synapses in the CA1 area of hippocampus and analyzed the expression levels of PSD95 and Shank1,two important synapseassociated proteins,in APPswe/PS1dE9 mice by immunohistochemical staining and western blot after gavage for three months.Results:Our findings showed that curcumin treatment not only improved the quantity and ultrastructure of synapses but also increased the expression of PSD95 and Shank1.Conclusion:The results indicate that curcumin improves synaptic dysfunction and the potential mechanism may involve improving the structure of synapses and regulating the synapse related proteins PSD95 and Shank1.