PSYCHOPATHOLOGY OF THE AGING: CELL MEMBRANE CORRELATES

这项研究方案使用荧光光谱作为工具来探测 血细胞和脑突触小体的生物物理特性 来自阿尔茨海默病患者的膜。(1)血小板的研究 红细胞膜可能会显示出特征性的变化，这可能有助于 阿尔茨海默病的死前诊断。被观察到的关系 阿尔茨海默病患者血细胞膜的变化 到人口统计学和临床(发病年龄、病程、严重程度、睡眠 将调查这一群体的脑电指标)特征。(2) 还将进行实验，以确定是否改变了 阿尔茨海默病患者的血细胞膜反映了一种全身性的血小板 或红细胞膜“缺陷”或这些细胞的年龄分布的改变 细胞。除了这一重要的澄清，这些实验将 提供有关伴随正常的细胞膜变化的信息 外周血细胞的衰老过程。(3)的功能后果 血小板膜的生物物理异常将通过 以血小板聚集为模型系统。(4)平行研究 从阿尔茨海默病新鲜未固定区域制备突触体膜 Brain将提供关于膜生物物理特性的信息，如 与组织病理学报告相关联。因此，这将是可能的 以确定这些突触小体中是否有任何已发现的变化 膜的特性比特性更普遍 阿尔茨海默病的组织病理学异常以及 细胞膜的改变可能会提前神经元的退化和细胞的丢失。 为了完成建议的研究计划，应聘者将获得 其他受监督经验：(1)血细胞和突触体 膜分离；(2)荧光理论与技术 光谱学；以及(3)临床的设计、实施和分析 研究性研究。

This research proposal employs fluorescence spectroscopy as a tool to probe the biophysical characteristics of blood cell and brain synaptosomal membranes from patients with Alzheimer's disease. (1) Studies of platelet and RBC membranes may reveal characteristic alterations that may aid in the antemortem diagnosis of Alzheimer's disease. The relationship of observed alterations in blood cell membranes from patients with alzheimer's disease to the demographic and clinical (age at onset, duration, severity, sleep EEG indices) characteristics of this group will be investigated. (2) experiments will also be conducted to determine whether alterations in blood cell membranes from Alzheimer patients reflect a generalized platelet or RBC membrane "defect" or a change in the age-distribution of these cells. In addition to this important clarification, these experiments will provide information on cell membrane changes that accompany the normal aging process of peripheral blood cells. (3) The functional consequence of biophysical abnormalities of platelet membranes will be determined using platelet aggregation as a model system. (4) A parallel study of synaptosomal membranes prepared from fresh, unfixed regions of Alzheimer brain will provide information on membrane biophysical properties as correlated with histopathologic reports. It will, therefore, be possible to determine whether any identified alterations in these synaptosomal membrane properties are more widespread than the characteristic histopathologic abnormalities of Alzheimer's disease and whether the membrane changes are likely to antedate neuronal degeneration and cell loss. To accomplish the proposed research plan, the candidate will obtain additional supervised experience in: (1) blood cell and synaptosomal membrane isolation; (2) the theory and techniques of fluorescence spectroscopy; and (3) the design, execution, and analysis of clinical research studies.