AMYLOID PEPTIDES IN CSF OF ALZHEIMER'S DISEASE

阿尔茨海默病脑脊液中的淀粉样肽

• 批准号: 3428833
• 负责人: PANKAJ D. MEHTA
• 金额: $ 4.01万
• 依托单位: INSTITUTE FOR BASIC RES IN DEV DISABIL
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3428833
• 关键词: Alzheimer's disease; amyloid proteins; biomarker; brain disorder diagnosis; cerebrospinal fluid; diagnosis design /evaluation; enzyme linked immunosorbent assay; human tissue; paired helical filament; synthetic peptide; Alzheimer's disease; amyloid proteins; biomarker; brain disorder diagnosis; cerebrospinal fluid; diagnosis design /evaluation; enzyme linked immunosorbent assay; human tissue; paired helical filament; synthetic peptide

Neuropathological examination of the brains from patients with Alzheimer's disease (AD) have revealed deposits of two types of abnormal fibers. These are the paired helical filaments making the neurofibrillary tangles and amyloid fibers in plaques and vessels. Several laboratories have provided evidence that the main protein component of both cerebrovascular and plaque amyloid is AD is beta-protein. Recently the molecular cloning and characterization of cDNAs encoding the beta-protein precursor have been reported. Structural studies of the protein indicates that the amyloid precursor protein is a cell surface protein. We have selected amino acid segments from regions of the protein that are thought to lie (a) outside the cell, (b) in the cell membrane and (c) in the cytoplasm. Three different peptides, each 19-24 amino acids in length, that correspond to these protein segments were synthesized by using an automated peptide synthesizer. Rabbit antisera are being produced against these carrier-linked synthetic peptides. Because amyloid proteins are degraded in the brains of AD patients, fragments may be found in CSF. Thus we propose to quantitate the level of synthetic peptides in CSF from patients with AD, using specific antisera to the peptides and a sensitive enzyme linked immunosorbent assay. Since there is no specific laboratory test for the diagnosis of AD, detection of higher levels of amyloidogenic peptides in CSF may be a useful marker in the diagnosis of the disease.

对患者的大脑的神经病理学检查 阿尔茨海默氏病（AD）揭示了两种类型的存款 异常纤维。 这些是配对的螺旋丝制作 斑块中的神经原纤维缠结和淀粉样纤维 船只。 几个实验室提供了证据表明 脑血管和斑块的主要蛋白质成分 淀粉样蛋白是AD是β-蛋白质。 最近分子克隆 和编码β-蛋白质的cDNA的表征 据报道了前体。 蛋白质的结构研究 表明淀粉样蛋白前体蛋白是细胞表面 蛋白质。 我们选择了来自 被认为躺在细胞外的蛋白质，（b） 细胞膜和（C）在细胞质中。 三种不同的肽， 每个19-24个氨基酸的长度，与这些蛋白质相对应 使用自动肽合成段 合成器。 兔子抗血清正在针对这些 载体连接的合成肽。 因为淀粉样蛋白是 在AD患者的大脑中降解，可能会发现碎片 CSF。 因此，我们建议定量合成水平 AD患者CSF中的肽，使用特定的抗血清 肽和敏感酶连接免疫吸附测定法。 由于没有特定的AD诊断实验室测试 检测CSF中较高水平的淀粉样蛋白肽可能 在诊断疾病中成为有用的标记。