Functional Change of Cytoskeletal Proteins in Dementia Brain

对阿尔茨海默病患者细胞骨架蛋白的变化进行了研究，并获得了以下实验数据.实验性铝中毒的神经细胞学改变本实验观察了铝中毒家兔脑内10nm纤维的产生。聚集的10 nm细丝由神经丝蛋白组成，并且聚集部分是由于神经丝亚单位蛋白的过量产生，部分是由于降解酶的活性受损。积累的神经丝蛋白过度磷酸化。提示神经丝蛋白从轴突向神经索马或树突的移位是铝中毒脑组织的主要病理过程.本文研究了阿尔茨海默病（Alzheimer 'sdisease，AD）患者血清中抗胶质细胞酸性蛋白（GFAP）抗体滴度。阿尔茨海默病血清显示出对GFAP的较高抗体滴度。该抗体的高滴度是诊断阿尔茨海默病的一个有用的生物学标志物.阿尔茨海默病成纤维细胞的细胞骨架畸变研究用阿尔茨海默成纤维细胞证明了粘附效率的降低。Alzheimer病成纤维细胞中波形蛋白的分布发生了异常，提示了一些影响细胞粘附和细胞因子分布的病理过程.本文提出了一种测量中间丝组装程度的荧光法。研究了GFAP的组装动力学，结果表明，这种新开发的方法产生可靠的评价GFAP的组装程度的真实的时间的基础上。

Changes in cytoskeletal proteins with Alzheimer's disease and investigated and the following experimental data have been obtained.1. Experimental neurofibrillary changes by aluminium intoxication The production of 10 nm filaments in the brain of aluminium intoxicated rabbit brain was studied. The accumulated 10 nm filaments are composed of neurofilament proteins and the accumulation is partly due to overproduction of neurofilament subunit proteins and partly by impaired activity of degradating enzymes. Accumulated neurofilament proteins are overphosphorylated. It is indicated dislocalization of neurofilament protein from axons to neural soma or dendrites is the main pathological process in aluminium intoxicated brain.2. Antibody titer against glial fibrillary acidic protein (GFAP) Autoantibody titer to cytoskeletal protein in sera from Alzheimer's disease patients were studied. Higher antibody titer to GFAP is shown with Alzheimer's disease serum. The high titer of this antibody is a useful biological marker of diagnosis of Alzheimer's disease.3. Cytoskeletal aberration of Alzheimer fibroblasts Fibroblasts cultured from Alzheimer's disease patients were studied. The decreased efficiency in adhesion was demonstrated with Alzheimer fibroblasts. Vimentin distribution in Alzheimer fibroblasts were aberrated and some pathological process is indicated which affects cell adhesion and the distribution of the cytoskeletons.4. Fluorometric method to measure the degree of assembly of intermediate filaments have been developed. Assembly kinetics of GFAP was studied and it is shown that this newly developed method produces reliable evaluation of the degree of assembly of GFAP on the real time basis.