PATHOLOGY OF FASCIA DENTATA IN ALZHEIMER'S DISEASE

神经炎性斑块是阿尔茨海默病和正常衰老的关键特征。 海马结构内的神经炎斑块具有非常显著的 特征性分布于齿状筋膜的分子层， 其中它们平行于颗粒细胞层排列。 如此精确， 可预测的模式提供了一个独特的机会， 定位方面的传入的分布， 分子层和形态学颗粒细胞树突。 两套 实验将测试的假设，在分布的变化， 传入和颗粒细胞形态的变化， 第一个斑块出现。 第三组实验将考察 小胶质细胞和淀粉样蛋白在斑块形成中的作用， 神经炎斑块的人群。 这些实验的最终目的是 为了开发作为模型系统的筋膜齿的分子层， 以研究阿尔茨海默氏症神经炎斑块的发病机制 疾病 首先，在控制和 老年痴呆症患者将与层状分布有关 神经炎斑块 每个Rapid将使用多个解剖标记 尸检案。 内嗅皮层的穿通路径 用荧光染料Dil标记。 胆碱能传入神经 基底前脑胆碱能核将用 乙酰胆碱酯酶组织化学 生长抑素和胆囊收缩素 传入神经将被化学标记。 第二，关系 将确定神经炎斑和颗粒细胞之间的关系。 细胞内注射荧光黄会填满树突树， 树突的分支模式和树突的病理学是有关联的 斑块的位置。 异常颗粒细胞体的分布 含有神经纤维缠结、Pick样小体或异常 神经丝抗原将与斑块的分布相关 在上面的分子层中。 第三，积累模式 小胶质细胞和淀粉样蛋白将与神经元中的上述变化相关， RCA-1凝集素组化标记小胶质细胞，刚果红染色 和淀粉样β蛋白免疫化学来标记淀粉样蛋白。 淀粉样 沉积也将与痴呆发作的年龄相关， 痴呆的持续时间和痴呆的家族史。

Neuritic plaques are a key feature of Alzheimer's disease and normal aging. Neuritic plaques 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 granule cell dendrites. Two sets of experiments will test the hypothesis that changes in the distribution of afferents and changes in the morphology of granule cells develop as the first plaques appear. The third set of experiments 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 markers 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 neuritic 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 immunochemistry to label amyloid. Amyloid deposition will also be correlated with the age of onset of dementia, duration of dementia, and family history of dementia.