STRUCTURAL PHYSIOLOGY, PATHOLOGY OF PLATELETS IN A.D.

公元后血小板的结构生理学、病理学

• 批准号: 3368679
• 负责人: JAMES G WHITE
• 金额: $ 19.36万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3368679
• 关键词: Alzheimer's disease; amyloid proteins; biochemistry; calcium flux; enzyme activity; granule; human tissue; immunocytochemistry; membrane proteins; membrane structure; pathology; platelets; prostaglandins

Alzheimer's disease (AD) platelets are the only cells in circulating blood to contain and secrete significant quantities of amyloid beta protein precursor (APP) found in abundance in senile plaques and neurofibrillary tangles, the lesions characteristically present in brains from AD patients. Our long term goal is to fully characterize the morphology, biochemistry and physiology of AD platelets and their relationship to the pathogenesis of the disease. Specifically, we will use ultrastructural immunocytochemistry to localize APP to alpha granules or other organelles in resting AD platelets and follow secretion of APP to the exterior following suspension activation or to subendothelium after surface activation. Micropipette elastimetry will determine if the increased fluidity of internal membranes is reflected in increased deformability of AD platelets. The nature of the internal membranes reported to accumulate in AD platelets will be determined by ultrastructural cytochemical procedures selective for the open canalicular system and dense tubular system. Effects of increased concentrations of APP and internal membrane accumulation on calcium flux, prostaglandin synthesis, and AD platelet function and structure during long-term storage will be studied in detail. We will also evaluate the influence of peptide homologues of APP on normal platelet structure, biochemistry and function. The proposed studies will provide the basic information essential to clarify the influence of increased APP and accumulated membranes on the pathophysiology of platelets in AD.

阿尔茨海默氏病（AD）血小板是循环血液中唯一的细胞 包含并分泌大量的淀粉样β蛋白 前体（APP）在老年斑块和神经纤维中发现 缠结，病变的特征是广告患者的大脑中。 我们的长期目标是充分表征形态，生物化学 AD血小板的生理及其与发病机理的关系 疾病。 具体而言，我们将使用超微结构 免疫细胞化学将应用程序定位到α颗粒或其他细胞器 在休息广告血小板并将APP分泌​​到外部 悬浮激活或表面下皮下皮 激活。 微孔弹性测定法将确定是否增加 内膜的流动性反映在增加 广告血小板。 据报道积累的内膜的性质 在广告中，血小板将由超微结构细胞化学确定 选择开放口管系统和密集管的程序 系统。 浓度增加的应用和内膜的影响 积累钙通量，前列腺素合成和AD血小板 长期存储期间的功能和结构将进行详细研究。 我们还将评估应用程序的肽同源物对正常的影响 血小板结构，生物化学和功能。 拟议的研究将 提供基本信息，以阐明 在血小板的病理生理学上增加了应用程序和累积的膜 在广告中。