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.

我们研究了使用血管损伤标记和APP的淀粉样β-蛋白蛋白前体（APP）和Arzheimer病（AD）和血管疾病（VD）的功能。血管损伤的活化标记。通常通过β-拥球蛋白等进行血小板激活倾斜血液样本的检测。但是，有一些关于敏感和特定测定方法的报道，例如流动眼测定分析。我们首先研究了血栓性疾病中APP和血小板衍生的微粒的关联，并且在脑梗塞，糖尿病和尿素病的患者中，APP阳性微粒的关联明显更大。这些结果表明，Micropartiele App可能对凝血的异常性有调节性影响，并且是血管损伤的新标志。因此，我们接下来研究在动脉粥样硬化患者中是否可以定量检测血小板激活，该患者通过临床严重程度进行了评分。在使用血管造影的严重程度诊断出严重程度的冠状动脉疾病的患者中，血小板激活特异性标记（例如P-选择蛋白（CD62P）和CD63）的表达显着增加，尤其是在三胞胎疾病中。我们的发现表明，血小板激活发生在严重的冠状动脉狭窄患者中。我们已经报道了App的纯化，Whoch是人类活化的Platclets AD病理生理学的关键物质之一。我们分别检测到冠状动脉疾病中XI因子的激活。该项目的结果表明，应用在没有相关的激活血小板表面表达。需要进行更多的研究来建立使用血小板激活来挖掘VD的新测定方法的开发。