AGING AND ALZHEIMER DEMENTIA: ROLE OF FIBROUS PROTEIN

这个项目的目的是了解生物化学，生物学和 阿尔茨海默病(AD)的分子病理机制。在这种混乱中， 主要的组织病理学损害是神经原纤维的存在。 大脑中的缠结和神经炎性斑块。阿尔茨海默氏神经原纤维 缠结(蚂蚁)被发现含有独特的抗原决定簇和 决定因素与几个正常的细胞骨架成分相同。这个 ANT和神经丝之间的关系将被进一步研究 通过确定核因子-核转录因子决定因素在 核因子分子。要使用的技术是有限的蛋白质分解，化学 核因子蛋白和免疫印迹的切割。正常和阿尔茨海默病中的三种蛋白质 分子量为58-70kd的脑匀浆最近被证明是 与抗蚂蚁单抗发生反应。这些产品的分布 正常和AD脑中的蛋白质及其与蚂蚁蓄积的关系 用酶联免疫吸附试验和免疫印迹技术进行研究。两种常见的核因子-蚂蚁 已发现抗原性决定簇对磷酸酶敏感。至 找出蚂蚁是否由磷酸化蛋白质组成，我们将从 阿尔茨海默病老年性痴呆死亡者的尸检脑 打字。将对提纯的样品进行磷酸盐含量研究。在……里面 此外，还将对它们进行钙和铝检测，这两种物质存在于 在缠结的神经元中浓度较高。金属元素将是 用能量色散x射线荧光法测定。我们的关注度也将 重点研究蚂蚁抗原的形态和生化特性 细小的神经元突起。电子显微镜和免疫电子显微镜 将用于确定抗原是否分布在丝状菌中 结构类似于PHF。我们还计划确定携带的抗原是否 结构和PHF一样抵抗增溶作用。最后 具体目的是调查啮齿动物和人类之间的关系 PFH，并研究细胞骨架在蓄积过程中的变化。 动物组织中的PHF。组织化学、电子显微镜和 将使用免疫电子显微镜。

This project is aimed at understanding the biochemistry, biology and molecular pathologenesis of Alzheimer's disease (AD). In this disorder, the main histopathological lesion is the presence of neurofibrillary tangles and neuritic plaques in the cerebrum. Alzheimer's neurofibrillary tangles (ANT) have been found to contain unique antigenic determinants and determinants in common with several normal cytoskeletal components. The relationship between ANT and neurofilaments (NF) will be examined further by identifying the topographical distribution of NF-ANT determinants in the NF molecules. The techniques to be used are limited proteolysis, chemical cleavage of NF proteins and immunoblots. Three proteins in normal and AD brain homogenates of molecular weight 58-70kd have recently been shown to react with monoclonal anti-ANT antibodies. The distribution of these proteins in normal and AD brain and their relation to ANT accumulation will be studied by ELISA and immunoblotting technique. Two NF-ANT common antigenic determinants have been found to be sensitive to phosphatase. To find out if ANT consist of phosphorylated proteins, we will purify ANT from autopsy brains of subjects who died of senile dementia of the Alzheimer type. The purified samples will be studied for phosphate content. In addition they will be assayed for calcium and aluminum which are present at high concentration in tangle bearing neurons. The metal elements will be determined by energy disperse x-ray fluorescence. Our attention will also focus on the morphological and biochemical properties of ANT antigens in fine neuronal processes. Electron microscopy and immunoelectron microscopy will be used to determine if the antigens are distributed in a filamentous structure similar to PHF. We also plan to determine if the antigen bearing structures are as resistant to solubilization as the PHF. The last specific aim is to investigate the relationship between rodent and human PFH, and to study the cytoskeletal changes proceeding the accumulation of PHF in animal tissue. Histochemistry, electron microscopy and immunoelectron microscopy will be used.