STUDY ON BIOCHEMICAL CHARACTERIZATION OF SENILE NEURONAL CYTOSKELETAL ABBERATION

点击翻译按钮获取中文摘要

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.