Objective To explore the association between PI3K polymorphisms in insulin signal transduction pathway and Alzheimer's disease (AD)risk.Methods There were three groups,including 112 cases for AD +T2D group,231 cases for only AD group,and 231 cases for healthy controls group.The polymorphisms in PI3K gene was sequenced by PCR and the concentration of PI3K in serum was tested by enzyme -linked immunosorbent assay (ELISA).Results Overall,there was significantly statistical difference in PI3K rs3730087 polymorphism among three groups (χ2 =20.99,P =0.000 3).The CC frequency of PI3K rs3730087 polymorphism in AD with T2D group and AD control group was significantly higher than that in the healthy control group.The PI3K protein level of differ-ent genotype was statistically significant (F =27.450,P <0.000 1).As for CC genotypes of PI3K rs3730087 poly-morphism,the PI3K protein level was statistically different among these three groups (F =8.096,P =0.000 6).Moreover,the PI3K protein level of the three groups was different (F =9.034,P =0.000 1),which in both AD group was lower as compared with healthy control group.Conclusion The study suggested that CC genotype of PI3K rs3730087 polymorphism in insulin signaling transduction pathway might be a risk factor for AD with T2D and it also affects the expression level of PI3K protein.However,the polymorphism is not shown to be exclusive in AD patients with T2D.