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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671934/
• 关键词: Arzheimer's disease; Cerebral infarction; Amyloid beta-protein precursor; Factor XI; Activated platelet; Flow eytometry; Coronary artery disease; 脳血管障害性痴呆; βアミロイド前駆体蛋白質; アルツハイマ-病; アミロイドbeta蛋白前駆体; 活性化凝固第XI因子

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.

我们利用血管损伤标志物和淀粉样β蛋白前体（APP）研究APP的功能及对阿尔茨海默病（AD）和血管病（VD）的诊断，并将APP与其他血小板活化标志物一起开发新的血管损伤诊断标志物。有一些敏感且特异的检测方法的报道，例如流式细胞仪分析。我们首先研究了APP和血小板衍生微粒在血栓性疾病中的相关性，并且APP阳性微粒在脑梗死、糖尿病和尿毒症患者中显著更大。结果提示，微粒APP可能对凝血功能异常有调节作用，可作为血管损伤的一个新的标志物。因此，我们接下来研究是否可以在动脉硬化患者中定量检测血小板活化，其根据临床严重程度分级。经冠状动脉造影确诊为冠心病的患者，血小板活化特异性标志物P-选择素（CD 62 P）、CD 63的表达均明显增高，尤以三支病变者明显。本实验室已报道了从人血小板中分离纯化出与AD病理生理有关的重要物质APP。并分别检测了冠心病患者凝血因子XI的激活情况。本实验结果提示，APP在活化血小板表面表达，且无释放。需要进一步研究建立新的AD检测方法，以通过血小板活化来鉴别VD。

项目成果

S.Nomura & Y.Komiyama et al.: "Amyloid beta-Protein Precursor-rich Microparticles in Thrombotic Disease" Thrombosis and Haemostasis. 72. 519-522 (1994)

野村

T.Murakami et al.: "Flow cytometric analysis of platelet activation markers CD62P and CD63 in patients with coronary artery disease" European Journal of clinical lnvestigation. 26. 996-1003 (1996)

T.Murakami 等人：“冠状动脉疾病患者血小板活化标记物 CD62P 和 CD63 的流式细胞术分析”《欧洲临床调查杂志》。

Y.Komiyama et al.: "Activated coagulation factors in Verious thrombotic diseases" Japanese Journal of Clinical Pathology. 43. 1195-1200 (1995)

Y.Komiyama 等人：“多种血栓性疾病中的活化凝血因子”日本临床病理学杂志。

T.Murakami and Y.Komiyama et al.: "Flow cytometric analysis of platelet activation markers CD62P and CD63 in patients with coronary artery discase" European Journal of Clinical Investigation. 26. 996-1003 (1996)

T.Murakami 和 Y.Komiyama 等人：“冠状动脉疾病患者血小板活化标记物 CD62P 和 CD63 的流式细胞分析”《欧洲临床研究杂志》。

S.Nomura & Y.Komiyama,et al.: "Amyloid β-Protein Precursor-rich Microparticles in Thrombotic Disease" Thrombosis and Haemostasis. 72. 519-522 (1994)

S. Nomura 和 Y. Komiyama 等人：“血栓性疾病中富含淀粉样 β-蛋白前体的微粒”《血栓形成和止血》72. 519-522 (1994)。