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Development of the Enzyme Immunoassay System for the Substances Related to the Pathogenesis of Alzheimer's Disease

阿尔茨海默病发病相关物质酶联免疫检测系统的研制

基本信息

批准号：
05557036
负责人：
HAYASHI Kyozo
金额：
$ 7.36万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Alzheimer's disease (AD) leads to a progressive and irreversible damage of memory and cognitive function in afflicted elderly individuals. AD is characterized by various pathological markers in the brain, chief of which are large amounts of amyloid plaques and neurofibrillary tangles and neuronal cell loss. Especially, cholinergic neurons of basal forebrain nuclei, which are important for cognitive functions, undergo degenerative changes in AD.Besides, in AD,the activety of acetylcholine esterase and choline acetyltransferase are reduece and, as a results, the amount of acetylcholine, a neurotransmitter, is also reduced. At present, litte is known about the relationship between AD and neurotrophic factors (NTFs) and other growth factors related to the pathogenesis of AD.The main reason seems to be lack of aboundance of these factors in most tissues, and lack of a method to reliably detect the protein levels of these factos. Purpose of this reseach was thus to develop the highly sentiti … More ve, specific enzyme immunoassay (EIA) systems for various NTFs and other cell growth factors related to the pathogenesis of AD and to apply these developed EIA systems for the diagnosis of the AD.Major results are summarized as follows :(1) we prepared anti-recombinant human NGF antibody IgG and characterized its properties immunologically. Using this antibody IgG,we developed a sentive two-site EIA system for human NGF.We measured NGF levels using this system and found no difference in NGF level in serum, brain-spinal fluid, or brain (hippocampus and parietal cortx) obtained from normal people and patients with AD.These results suggest that a decrease in the NGF level is not causative factor of AD.(2) We developed an EIA system for NT-3, based on a biotin-streptoavidin detection system capable of measureing concentrations as low as 0.5 pg/ml with high reproducibility. We measured NT-3 levels in the developing rat nervous system as well as in normal subjects and patients with AD.The developmental changes of NT-3 level in rat brain and peripheral tissues coincided with the changes in NT-3 mRNA level reported before. We could not find any differences in NT-3 level in serum, cerebrospinal fluid, or brain (hippocampus and parietal cortex) obtained from controls and patients with AD. Less

阿尔茨海默病（AD）导致受折磨的老年个体的记忆和认知功能的进行性和不可逆的损害。AD以脑内多种病理标志物为特征，其中主要是大量淀粉样斑块和神经元缠结以及神经元细胞丢失。尤其是对认知功能起重要作用的基底前脑核团胆碱能神经元在AD时发生退行性改变，乙酰胆碱酯酶和胆碱乙酰转移酶活性降低，神经递质乙酰胆碱含量减少。目前，对AD与神经营养因子（neurotrophic factors，NTFs）及其他与AD发病相关的生长因子的关系知之甚少，其主要原因可能是这些因子在大多数组织中缺乏丰度，且缺乏可靠的方法检测这些因子的蛋白水平。因此，这项研究的目的是开发高度敏感的 ...更多信息建立了多种与AD发病相关的神经营养因子和其他细胞生长因子的特异性酶免疫分析（EIA）系统，并将其应用于AD的诊断。主要结果如下：（1）制备了抗重组人NGF抗体IgG，并对其免疫学特性进行了鉴定。用此抗体IgG建立了一种灵敏的人NGF双位点酶免疫测定系统，测定了正常人和AD患者血清、脑脊液和脑组织（海马和顶叶皮质）中的NGF水平，结果表明，NGF水平的降低不是AD的致病因素。(2)我们开发了一种基于生物素-链亲和素检测系统的NT-3 EIA系统，该系统能够测量低至0.5 pg/ml的浓度，具有高重现性。本研究测定了发育中大鼠神经系统、正常人和AD患者的NT-3水平，结果表明，大鼠脑及周围组织中NT-3水平的发育性变化与文献报道的NT-3 mRNA水平的变化相一致。我们在对照组和AD患者的血清、脑脊液或大脑（海马和顶叶皮质）中未发现NT-3水平有任何差异。少