Objective To investigate the changes of the platelet function in APP/PS-1/tau(3xTg) mice, a murine model for Alzheimer's disease,and explore its mechanisms. Methods We assessed the change of function of platelet in 3xTg-AD mice by flow cytometry. Adhesion assay and Western blotting were used to compare with the data of wild type mice. Results Platelets from aged 3xTg-AD mice were normal in number and glycoprotein expression (P> 0.05), but adhere more avidly on matrices such as fibrinogen, compared with the platelets from age-matching wild type mice (P<0.05). The washed platelets of 3xTg-AD mice were adherent to fibrinogen, and also showed increased phosphorylation of selected signaling proteins, including PI3 kinase effector Akt and p38MAP kinase (P<0.05). In contrast, activation induced by several agonists in 3xTg-AD mice was similar to that of wild type platelets (P>0.05). Conclusions These results demonstrate that Alzheimer's mutations result in a significant hyper-activated adhesion state of circulating platelets, evident with the progression of the disease.