DIAGONAL BAND--ORGANIZATION AND CHANGES IN DEMENTIA

对角带——痴呆症的组织和变化

• 批准号: 3078589
• 负责人: HARRY R BRASHEAR
• 金额: $ 6.61万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3078589
• 关键词: Alzheimer's disease; GABA receptor; autoradiography; brain mapping; central neural pathway /tract; cholinergic receptors; electron microscopy; histochemistry /cytochemistry; human tissue; immunochemistry; inclusion body; laboratory rat; neural degeneration; neuroanatomy; neurofibrillary tangles; neurons; neurotransmitters; postmortem; silver impregnation

Cognitive impairment in the elderly is a major health, social and economic problem affecting about 15% of the population over age 65. Over half of these cases are due to dementia of the Alzheimer's type (DAT). This proposal focuses on the diagonal band of Broca (DB), a part of the basal forebrain projection system known to be prominently involved in Alzheimer's disease, and asks two basic questions: (1) what is the anatomical organization of the DB which may predispose it to Alzheimer's pathology? (2) what specific changes occur in the DB and how do they contribute to the pathogenesis of Alzheimer's disease? The question of a causal relationship between cortical pathology and basal forebrain degeneration in DAT needs to be resolved. The DB provides cholinergic innervation to specific brain regions which consistently show marked pathology and cholinergic deficit in DAT. This work will use quantitative autoradiography, histochemistry, morphometry, Golgi impregnation and electron microscopy to study DB changes in DAT. Combined methods will be used to determine the role of human DB neurons in the pathogenesis of neuritic plaques and neurofibrillary tangles. Studies of the normal cellular structure, neurotransmitter content and connectivity of the DB will be extended to test the hypothesis that the organization of the DB resembles the reticular formation and provides widespread innervation of limbic structures. Combined techniques will be applied to determine if parallel cholinergic and GABAergic projection systems are a consistent feature in the DB, to elucidate the nature of an intrinsic DB network and to characterize synaptic input fat the ultrastructural level. Results of this work will provide a more clear understanding of the anatomical organization of the basal forebrain, insight into the vulnerability of the basal forebrain cholinergic system and evidence for the mechanism of cellular injury in Alzheimer's disease.

老年人的认知障碍是一种主要的健康，社会和 经济问题影响约15％以上的人口 65。超过一半是由于痴呆症 阿尔茨海默氏症类型（dat）。 该提议重点是对角线 Broca（DB）的乐队，基础前脑投影的一部分 已知系统参与阿尔茨海默氏病， 并提出两个基本问题：（1）解剖学是什么 DB的组织可能使其易于使用阿尔茨海默氏症 病理？ （2）数据库中发生了哪些具体变化以及如何 它们有助于阿尔茨海默氏病的发病机理？ 皮质病理之间因果关系的问题 DAT中的基础前脑变性需要解决。 DB为特定的大脑区域提供胆碱能神经 始终显示出明显的病理和胆碱能赤字 在dat。 这项工作将使用定量自显影术， 组织化学，形态计量学，高尔基体浸渍和电子 研究DB变化的显微镜。 合并的方法将 用于确定人DB神经元在 神经斑块和神经原纤维缠结的发病机理。 正常细胞结构，神经递质含量的研究 DB的连通性将扩展以检验假设 DB的组织类似于网状形成 并提供了边缘结构的广泛支配。 合并技术将应用于确定是否平行 胆碱能和GABA能投影系统是一致的 DB中的特征，以阐明固有DB的性质 网络并表征突触输入脂肪 超微结构水平。 这项工作的结果将提供更清楚的了解 基础前脑的解剖组织，洞察 基础前脑胆碱能系统的脆弱性和 阿尔茨海默氏症细胞损伤机制的证据 疾病。