Development of iagnostic tool of Arzheimer's discase with use of platelet factor XI and Amyloid beta-protein precursor

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We investigated the function of Amyloid beta-protein precursor (APP) and diagnosis for Arzheimer's disease (AD) and vascular disease (VD) with use of vascular injury markers and APP.And we developed the new diagnostic markers with use of APP and other platelet activation markers for vascular injury.The detection of platelet activation inclinical blood sample was generally performed by beta-thromboglobulin and so on. However, there was a few reports of sensitive and specific assay methods, such as flow eytometric analysis. We first investigated the association of APP and platelet derived microparticles in thrombotic diseases, and APP-positive microparticles was significantly greater in the patients with cerebral infarction, diabetes, and uremia. These results suggested that micropartiele APP may have a regulatory influence on coagulation abonormality and be a new marker for vascular injury. Therefore, we next investigate whether platelet activation could be quantitatively detected in the patients with arteriosclerosis, which were graded by clinical severity. In the patients with coronary artery disease, who were diagnosed the severity with use of angiography, the expression of platelet activation specific markers such as p-selectin (CD62P) and CD63 were significantly increased and especially in three-vessel disease. These our findings indicate that platelet activation occurs in the patients with severe coronary artery stenosis.We already reported the purification of APP,whoch was one of the key substances of the pathophysiology of AD,from human activated platclets. And we separately detected the activation of factor XI in coronary artery disease. The results in this project suggested that APP expressed on the surface of activated platelet without relcase. More study is needed to establish the development of new assay method for the AD to distiguish VD using platelet activation.