PARKINSON DISEASE PATHOPHYSIOLOGY--CSF MARKERS

帕金森病病理生理学--脑脊液标志物

• 批准号: 3414333
• 负责人: PETER A LEWITT
• 金额: $ 12.75万
• 依托单位: SINAI HOSPITAL OF DETROIT
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414333
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; Parkinson's disease; adult human (21+); aging; aminoacid; antibody; antioxidants; antiparkinson drugs; biomarker; cerebrospinal fluid; cholecystokinin; cognition disorders; copper; deprenyl; disabling disease; disease /disorder proneness /risk; endorphins; enkephalins; gamma aminobutyrate; gel electrophoresis; high performance liquid chromatography; histochemistry /cytochemistry; homovanillate; human subject; hydroxyindoleacetate; immunopathology; mesencephalon; neurochemistry; neuropsychology; neurotransmitters; pathology; prognosis; proteins; pteridines; radioimmunoassay; somatostatin; spectrometry; tocopherols; vitamin therapy

Though its clinical picture and brain pathology (loss of nigrostriatal dopaminergic projections) are distinctive, Parkinson Disease (PD) is associated with few biological markers that can be studied in life. Several abnormalities in PD have been found in cerebrospinal fluid (CSF) constituents, among them, monoamine neurotransmitter metabolites (HVA, 5- HIAA, and MHPG), GABA and other amino compounds, pteridines, copper, specific proteins on 2-dimensional gel electrophoresis, and immunoreactivities recognizing CCK, somatostatin, beta-endorphin, and met- enkephalin. In addition, antibodies against mesencephalic neurons will be analyzed and characterized. This study will systematically investigate these neurochemical clues, in correlation with an intensive PD assessment database collected from 150 unmedicated subjects, aged 30-70 and in early stages of PD. CSF will be obtained on 2 occasions up to 25 months apart; specimens will also be collected and studies from normals matched to the parkinsonians' 5 decade age-span. The utility of these substances in differentiating PD from controls, and milder from more severe parkinsonism will be investigated. Analyses will also be focused on correlations between these constituents and specific features (clinical, demographic, and neuropsychological) of PD and its sub-types, as well as to rate of progression and other clinical outcomes of the unmedicated disorder. These CSF markers represent a diversity of neurochemical clues whose significance in the natural history of the disorder remains to be determined. Certain of these CSF substances may be correlated of severity or specific clinical features of PD (and so might have prognostic applications), while others might prove to be markers of risk or lifelong trait of PD (which would be extremely valuable for studying familial patterns or pre-clinical stages of this disorder). If these study goals are achieved, there would also be important implications for an ongoing study of deprenyl and tocopherol in PD. Should this 800 patient therapeutic trial (the source of CSF specimens and the clinical database for the proposed study) provide evidence that anti- oxidative therapy can avert further development of parkinsonism, then those CSF traits or state markers which are altered in the treatment- responsive group might provide insight into the mechanism(s) for initiation and progression of PD.

虽然其临床表现和脑病理(黑质纹状体缺失) 多巴胺能投射)是独特的，帕金森病(PD)是 与生活中可以研究的生物标记物很少相关。 在脑脊液中发现了一些帕金森病的异常。 成分，其中单胺类神经递质代谢物(HVA，5- HIAA，和MHPG)，GABA和其他氨基酸化合物，蝶类，铜， 双向凝胶电泳法检测特定蛋白质，以及 识别CCK、生长抑素、β-内啡肽和MET的免疫反应 脑啡肽。此外，针对中脑神经元的抗体将是 对其进行了分析和表征。本研究将系统地研究 这些神经化学线索，与密集的帕金森病评估相关 数据库来自150名年龄在30-70岁及早期未服药的受试者 帕金森病分期。两次采集脑脊液，间隔最长25个月； 还将收集样本并研究与之匹配的正常人 帕金森氏症患者的50岁年龄跨度。这些物质在人体内的用途 区分帕金森病与对照组、轻度与重度帕金森病 将会被调查。分析还将重点放在相关性上 在这些构成要素和特定特征(临床、人口统计学、 和神经心理学)，以及帕金森病及其亚型的发生率 未用药障碍的进展和其他临床结果。 这些脑脊液标志物代表了多种神经化学线索，这些线索 这种疾病在自然历史上的意义仍有待于 下定决心。这些脑脊液物质中的某些物质可能与严重程度相关 或帕金森病的特定临床特征(因此可能具有预后 应用程序)，而其他应用程序可能被证明是风险或终身的标志 帕金森病的特点(这对于研究家族性帕金森病是非常有价值的 模式或临床前阶段 这种障碍)。如果实现了这些研究目标，还将有 一项正在进行的丙烯基和生育酚研究的重要意义 警察。 这800名患者治疗试验(脑脊液样本来源和 拟议研究的临床数据库)提供的证据表明 氧化疗法可以避免帕金森症的进一步发展，然后 在治疗中改变的脑脊液特征或状态标记物- 响应小组可能提供对以下机制的洞察(S) 帕金森病的发生和发展。