PATHOLOGY OF FASCIA DENTATA IN ALZHEIMERS DISEASE

阿尔茨海默病筋膜齿状病理学

• 批准号: 3120993
• 负责人: BARBARA J CRAIN
• 金额: $ 11.27万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-15 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3120993
• 关键词: Alzheimer's disease; aging; amyloid proteins; cholecystokinin; confocal scanning microscopy; dendrites; dentate gyrus; fluorescent dye /probe; hippocampus; histopathology; human tissue; immunocytochemistry; microglia; neural degeneration; neuritic plaques; neurofibrillary tangles; neurofilament; neuronal guidance; neuropil; pathology; postmortem; silver impregnation; somatostatin; surface antigens

Neuritic plaques are a key feature of Alzheimer's disease and normal aging. Neuritic plaque within the hippocampal formation have a very characteristic distribution in the molecular layer of the fascia dentata, where they are aligned parallel to the granule cell layer. This precise predictable pattern provides a unique opportunity to define plaque localization in terms of both the distribution of afferents to the molecular layer and the morphology of granule cell dendrites. Two sets of experiments will test the hypothesis that changes in the distribution of afferents and change in the morphology of granule cells develop as the first plaques appear. The third set of experiment will examine the role of microglia and amyloid in plaque formation in this well-defined population of neuritic plaques. The ultimate goal of these experiments is to develop the molecular layer of the fascia dentata as a model system in which to examine the pathogenesis of neuritic plaques in Alzheimer's disease. First, the distribution of afferents to the molecular layer in control and Alzheimer's disease patients will be related to the laminar distribution of neuritic plaques. Multiple anatomic marker will be used in each Rapid Autopsy case. The perforant path from the entorhinal cortex will be labeled with the fluorescent dye Dil. The cholinergic afferents from the basal forebrain cholinergic nuclei will be labeled with acetylcholinesterase histochemistry. Somatostatin and cholecystokinin afferents will be labeled immunohistochemically. Second, the relationships between the neuritin plaques and the granule cells will be defined. Intracellular injections of Lucifer yellow will fill the dendritic trees so that dendritic branching patterns and dendritic pathology can be correlated with plaque location. The distribution of abnormal granule cell bodies containing neurofibrillary tangles Pick-like bodies, or abnormal neurofilament antigens will be correlated with the distribution of plaques in the overlying molecular layer. Third, patterns of accumulation of microglia and amyloid will be related to the above changes in the neuropil, using RCA-1 lectin histochemistry to label microglia and Congo red staining and amyloid beta protein immunohistochemistry to label amyloid. Amyloid deposition will also be correlated with the age of onset of dementia, duration of dementia and family history of dementia.

神经斑是阿尔茨海默氏病和正常衰老的关键特征。 海马形成中的神经斑块具有非常特征 在筋膜的分子层中的分布，它们在那里 平行于颗粒细胞层对齐。 这种确切的可预测 模式为定义斑块本地化提供了独特的机会 传入分子到分子层和 颗粒细胞树突的形态。 两组实验将测试 传入分布的变化和变化的假设 颗粒细胞的形态随着第一批斑块的出现而发展。 这 第三组实验将检查小胶质细胞和淀粉样蛋白在 在这个明确定义的神经斑块中形成斑块。 这 这些实验的最终目标是开发 筋膜Dentata作为模型系统，在其中检查 阿尔茨海默氏病的神经斑块。 首先，在对照中传入到分子层的分布和 阿尔茨海默氏病患者将与 神经斑块。 在每个快速中将使用多个解剖标记 尸检案例。 来自内嗅皮层的穿孔路径将是 用荧光染料DIL标记。 来自 基础前脑胆碱能核将标记为 乙酰胆碱酯酶组织化学。 生长抑素和胆囊动蛋白 传入将以免疫组织化学标记。第二，关系 将定义神经蛋白斑块和颗粒细胞之间。 Lucifer黄色的细胞内注射会填充树突状树 树突分支模式和树突状病理可以相关 有牌匾位置。 异常颗粒细胞体的分布 包含神经纤维缠结的拾取物或异常 神经丝抗原将与斑块的分布相关 在上覆的分子层中。 第三，积累的模式 小胶质细胞和淀粉样蛋白将与上述神经上的变化有关， 使用RCA-1凝集素组织化学标记小胶质细胞和刚果红染色 和淀粉样蛋白β蛋白免疫组织化学以标记淀粉样蛋白。 淀粉样蛋白 沉积也将与痴呆症的发作年龄相关， 痴呆症的持续时间和痴呆家族史。