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

使用血小板因子 XI 和淀粉样 β 蛋白前体开发阿茨海默病诊断工具

基本信息

批准号：
05671934
负责人：
KOMIYAMA Yutaka
金额：
$ 1.28万
依托单位：
KANSAI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

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.

应用血管损伤标志物和APP研究了淀粉样蛋白前体（APP）的功能及对阿尔茨海默病（AD）和血管疾病（VD）的诊断，并利用APP和其他血小板活化标志物开发了新的血管损伤诊断标志物。临床血样中血小板活化的检测一般采用β -凝血球蛋白等方法。然而，有一些报告的敏感和特异性的分析方法，如流式细胞法分析。我们首先研究了APP和血小板衍生微粒在血栓性疾病中的关联，发现APP阳性微粒在脑梗死、糖尿病和尿毒症患者中显著增加。提示微颗粒APP可能对凝血异常具有调节作用，可作为血管损伤的新标志物。因此，我们下一步研究是否可以在动脉硬化患者中定量检测血小板活化，并根据临床严重程度进行分级。在冠脉病变患者中，经血管造影诊断其严重程度时，血小板活化特异性标志物如p-选择素（CD62P）和CD63的表达明显升高，特别是在三支血管病变中。我们的研究结果表明，血小板活化发生在严重冠状动脉狭窄的患者。APP是AD病理生理的关键物质之一，我们已经报道了从人活化血小板中纯化APP的方法。我们分别检测了冠状动脉疾病中因子XI的激活。本项目结果提示APP在活化血小板表面表达无释放。建立一种新的检测方法，利用血小板活化来区分AD，还需要更多的研究。