PATHOLOGY OF FASCIA DENTATA IN ALZHEIMERS DISEASE

神经性斑块是阿尔茨海默病和正常衰老的关键特征。 海马体结构内的神经炎性斑块有一个非常典型的特征 它们在齿状筋膜分子层中的分布 与颗粒细胞层平行排列。这一精确的可预测 模式为定义斑块定位提供了独特的机会 关于传入分子层的分布和分子层的 颗粒细胞树突的形态。两组实验将测试 该假说认为传入神经分布的变化和 当第一个斑块出现时，颗粒细胞的形态就会发展。这个 第三组实验将检测小胶质细胞和淀粉样蛋白在 在这组明确的神经炎斑块中形成斑块。这个 这些实验的最终目标是开发出分子层 齿状筋膜作为模型系统研究牙周炎的发病机制 阿尔茨海默病的神经炎斑块。 第一，对照和对照中传入神经在分子层的分布 阿尔茨海默病患者脑组织的层状分布将与 神经炎斑块。每个快速应用程序将使用多个解剖标记 验尸案。从内嗅觉皮质开始的穿支路径将是 用荧光染料Dil标记。胆碱能传入神经 基底前脑胆碱能核团将被标记 乙酰胆碱酯酶组织化学。生长抑素与缩胆囊素 传入神经将被免疫组织化学标记。第二，人际关系 神经素斑块和颗粒细胞之间的关系将被定义。 细胞内注射荧光黄将填充树突树，因此 树突状分支模式和树突状病理可以关联 有斑块的位置。异常颗粒细胞体的分布 含有神经原纤维缠结的挑状小体，或异常 神经丝抗原将与斑块的分布相关联 在上面的分子层中。第三，积累的模式 小胶质细胞和淀粉样蛋白将与神经纤维的上述变化有关， RCA-1凝集素组织化学标记小胶质细胞和刚果红染色 淀粉样β蛋白免疫组织化学标记淀粉样蛋白。淀粉样蛋白 沉积也将与痴呆症的发病年龄相关， 痴呆病程和痴呆症家族史。

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.