STUDY ON BIOCHEMICAL CHARACTERIZATION OF SENILE NEURONAL CYTOSKELETAL ABBERATION

目的是建立脑血管性痴呆的动物模型。用一种新设计的夹子使沙土鼠双侧颈动脉狭窄。局部脑血流量连续8周下降至原来水平的75%。被动回避试验学习障碍。海马蔡区神经元死亡的少量形态证据。减少微管相关蛋白(HAP)的含量。2作为阿尔茨海默病的神经化学模型。给兔子注射铝盐。导致实验性神经原纤维改变的形成。对实验性神经原纤维改变的兔脑进行了研究，并测定了7种溶酶体酶的活性。表现出组织蛋白酶D酶的活性增加。用亲和层析法从注射铝的兔脑中纯化组织蛋白酶D酶。病理性组织蛋白酶D的分子和酶学性质表明其具有相同的分子量。氨基酸组成相同。但Km和Vmax值不同，热变性方式不同。此外，在老年大鼠脑中发现了溶酶体膜的不稳定性，这可能部分解释了组织蛋白酶D在阿尔茨海默病模型动物中活性升高的原因。对阿尔茨海默病患者血清中抗胶质纤维酸性蛋白自身抗体效价进行了测定，结果表明阿尔茨海默病患者血清中抗胶质纤维酸性蛋白抗体效价显著升高，而健康对照组血清中抗胶质纤维酸性蛋白自身抗体效价无明显变化。

Under the purpose of establishing an animal model of cerebrovascular dementia. the bilateral carotid artery of Mongolian gerbil is stenosed with a newly designed clip. showing decreased regional cerebral blood flow to 75 % of the original level for 8 weeks. dysfunction in learning by passive avoidance test. a little morphological evidence of neuronal death in hippocampal caI region. and decreased amount of microtubule-associated protein (HAP) 2.As a neurochemical model of Alzheiemr's diease. rabbits are injected with aluminium salt. resulting in formation of experimental neurofibrillary change. The rabbit brain with experimental neurofibrillary change is studied and the activity of seven lysosomal enzymes is assaged. showing increased activity of cathepsin D enzyme. The cathepsin D enzyme from the aluminium injected rabbit brain is purified by affinity chromatography. The molecular and emzymological characterization of the pathological cathepsin D shows the same molecular weight. same amino acid composition. but different Km and Vmax values, and different pattern of heat denaturation. Further, the instability of the lysosome membrame is demonstrated in the aged rat brain, which could partially explain the increased activity of cathepsin D in model animal of Alzheimer's disease.Under the purpose of finding a biological marker of Alzheimer's disease. the serum autoantibody titer to glial fibrillary acidic protein (GFAP) is assayed, showing significantly increased antibody titer to GFAP in Alzheimer's disease patient sera but not in that of the healthy control subjects.