MAPPING OF NEUROPATHOLOGY IN HEALTHY AGING AND DEMENTIA

健康老龄化和痴呆症的神经病理学图谱

• 批准号: 6563254
• 负责人: JOSEPH L PRICE
• 金额: $ 17.85万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563254
• 关键词: Alzheimer's disease; aging; amyloid proteins; astrocytes; brain mapping; disease /disorder onset; entorhinal cortex; hippocampus; histopathology; human old age (65+); human tissue; immunocytochemistry; neural degeneration; neuritic plaques; neurofibrillary tangles; neuropathology; paired helical filament; postmortem; prefrontal lobe /cortex; tau proteins

This project is closely related to the overall research goal of this program project, namely to define the behavioral and biomedical correlates of the clinical course of a defined group of subjects with SDAT (or in this project, with neuropathologically proven Alzheimer's disease) in comparison with the course of healthy aging in non-demented subjects. The specific goals of the project can be expressed as two questions (1) What pattern of pathology is characteristic of the earliest stage of Alzheimer's disease? (2) what is the relationship between the patterns of tangles and placques seen in healthy aging and in the earliest, very mild stage of dementia? To address these questions, the distribution and density of neurofibrillary tangles, amyloid placques and related immunohistochemical markers (e.g. with antibodies counted in serial sections cut through the ventral forebrain from a range of carefully assessed non-demented and demented elderly cases. The presence or level of dementia in these cases will be determined in the clinical core, either by pre-mortem assessment , or by a retrospective, post-mortem interview with a closely related collateral source (usually a spouse or adult child). Because results from the previous grant period indicate that he earliest pathological changes related to Alzheimer's disease must be found in cases that have not yet shown any clinically detectable dementing change, emphasis will be placed on very old non-demented cases. In these cases special attention will be given to small patches of "primitive" or "diffuse" placques in the temporal or orbital neocortex that were identified in non-demented cases during the previous grant period, and which may represent the earliest deposition of amyloid. To examine a possible link between early plaque and tangle formation, immunohistochemistry with antibodies against tau and related proteins (e.g. the antibody Alz-50) will be used to stain the region of plaques for altered neurites ("neuropil threads") that might represent an early neurotoxic reaction to amyloid deposition.

本项目与本课题的总体研究目标密切相关 计划项目，即定义行为和生物医学 确定一组受试者的临床病程与 SDAT（或在这个项目中，神经病理学证明的阿尔茨海默病 疾病）与非痴呆患者健康衰老过程的比较 科目。 该项目的具体目标可以表述为两个 问题 (1) 最早的病理学特征是什么？ 阿尔茨海默病的阶段？ (2) 两者之间有什么关系 在健康衰老和衰老过程中看到的缠结和斑块的模式 痴呆症的最早、非常轻微的阶段？ 为了解决这些问题，分布和密度 神经原纤维缠结、淀粉样斑块和相关免疫组织化学 标记（例如，在连续切片中计数的抗体 腹侧前脑来自一系列经过仔细评估的非痴呆和 老年痴呆症病例。 这些病例中痴呆症的存在或程度 将通过验尸前评估在临床核心中确定 ，或者通过对密切相关的人进行回顾性事后访谈 抵押来源（通常是配偶或成年子女）。 因为结果 从上一个资助期来看，表明他最早的病理学 必须在患有阿尔茨海默病的病例中发现与阿尔茨海默病相关的变化 尚未显示任何临床可检测的痴呆变化，重点将 放置在非常古老的非痴呆病例上。 在这些情况下特别 将关注“原始”或“扩散”的小块 颞或眶新皮质中的斑块在 上一个资助期内的非痴呆病例，并且可能 代表淀粉样蛋白的最早沉积。 检查可能的链接 早期斑块和缠结形成之间，免疫组织化学 抗 tau 蛋白和相关蛋白的抗体（例如抗体 Alz-50） 将用于对斑块区域进行染色以发现改变的神经突 （“神经纤维线”）可能代表早期神经毒性反应 至淀粉样蛋白沉积。