Common pathogenesis of type 2 diabetes and Alzheimer's disease:a potential mechanism

AIM: Some epidemiologic evidences suggest an association between type 2 diabetes mellitus(T2DM) and Alzheimer disease(AD).The present study was designed to explore the common pathogenesis in these two diseases by comparing the pathological changes in pancreas and hippocampus,the activity of glucogen synthase kinase 3β(GSK-3β) and protein phosphatase 2A(PP2A) in T2DM rats with those in AD rats.METHODS: The SD rats were fed with high glucose,high fat and high protein for 8 weeks,and then injected with streptozocin(STZ) to establish the T2DM models.The model of AD was made by injection of STZ in hippocampus.The levels of hyperphosphorylated tau protein and β-amyloid protein(Aβ) in hippocampus and pancreas were analyzed by Western blotting and immunochemistry.The activities of GSK-3β and PP2A were determined by using γ-32P-ATP and the specific peptide substrate.RESULTS: In hippocampus of T2DM rats,the tau protein was hyperphosphorylated,the Aβ level was raised,the activity of PP2A was increased and the activity of GSK-3β was decreased,which were also observed in the hippocampus of AD rats.In the AD rats,the Aβ level in pancreas was found to rise,the activity of PP2A decreased and the activity of GSK-3β increased,which were similar to the changes in pancreas of T2DM rats.However,tau protein was not detected in the pancreas of both groups.CONCLUSION: These findings suggest that there are some common pathological changes between T2DM and AD.The hyperphosohorylation of tau protein in hippocampus,the raised Aβ level in hippocampus and pancreas,as well as the corresponding activities of PP2A and GSK-3β may contribute to the pathogenesis in the development of T2DM and AD.