Effect of Curcumin on Production and Degradation of Aβ in APPswe/PS1dE9 Double Transgenic Mice

Objective To observe the effect of curcumin on the expression of Aβ synthase and Aβ-degrading enzyme IDE in APPswe /PS1dE9 double transgenic mice and investigate the mechanisms of curcumin in prevention and treatment of Alzheimer's disease (AD).Methods 3-month old APPswe /PS1dE9 dtg mice were randomly divided into model group,positive control group (Rosiglitazone group,0.92 mg /kg·d) and high dose curcumin (400 mg /kg·d),moderate dose (200 mg /kg·d) and low dose (100 mg /kg·d) groups (n=10),with C57BL /6J mice of the same age and genetic background as normal control group,n=10.Medication was given once a day by intragastric administration while the model group and normal control group received an equal volume of 0.5% carboxymethyl cellulose.After 3 months,Morris water maze was used to assess the learning and memory abilities of animals,and the changes of expression of hippocampal Aβ synthetase and PS2-degrading enzyme IDE were detected by immunohistochemistry.Results The behavior test revealed that most model mice showed peripheral type swimming,while the mice of normal control,positive control,high dose curcumin,moderate dose and low dose groups showed trend type and linear type swimming.The immunohistochemical staining of the expression of Aβ42 synthetase and PS2 degrading enzyme IDE showed that PS2positive cells in the hippocampal CA1 area were significantly increased in model mice compared with those in the normal control group (P0.01).Compared with the model group,PS2-positive cells in hippocampal CA1 area of all curcumin groups were significantly decreased (P0.01),that in model mice was increased in the normal control group (P0.05),and the average gray value of positive cells in low dose curcumin group was significantly increased compared with that in the model group (P0.01).IDE-positive cells in the hippocampal CA1 area were significantly decreased in the model mice than that in the normal control group (P0.01).Compared with the model group,IDE-positive cells in the hippocampal CA1 area were significantly increased in the moderate dose curcumin group (P0.05).The average gray value of IDE-positive cells in hippocampal CA1 area was significantly increased in the model mice compared with that of normal control group (P0.01),and the average gray value of IDE-positive cells in hippocampal CA1 area was significantly lower in all curcumin groups compared with that in the model group (P0.01).Conclusion Curcumin can improve the learning and memory abilities of APPswe /PS1dE9 doublet transgenic mice through decreasing the expression of Aβ synthetase and increasing the expression of Aβ-degrading enzyme,thus decreasing the expression of Aβ protein.