AMYGDALA IN ALZHEIMER'S DISEASE AND NORMAL AGING

这项研究的总体目标是阐明形态学 人类杏仁核神经元的关系和改变 对正常老年人和老年痴呆症患者的尸检 疾病（AD）。 杏仁核在大脑中占据着重要的位置， 边缘系统的电路，维持皮层之间的连接， 位于皮质下的联合区和内脏相关核， 并且在AD中经历严重的病理改变。 第一个目标是 确定AD引起的病理学改变是否具有 对特定杏仁核的偏爱。 初始形态测量 分析试图确定AD患者的杏仁核萎缩是否与 神经元堆积密度降低，神经元大小或神经元 损失 神经炎斑块（NPs）的地形分布， 将使用硫磺素S绘制神经纤维缠结（NFT），以测试 某些杏仁核是选择性脆弱的假说 在AD中。 重度、中度和可忽略水平的杏仁核 将在超微结构水平上选择性地研究病理学， 确定正常和病理改变之间的突触关系 结构，并确定是否改变突触长度和 突触密度与AD相关。 第二个目标是确定 皮质和杏仁核投射神经元NFT之间的关系， 以及在它们各自的终端字段中的几个中的NP。 数据从 颞叶皮质区，包括海马 与杏仁核连接相关的皮层下核团 将被用来测试在发病机制中的跨神经元效应， AD. 第三个目标需要使用实验性神经解剖技术 以确定内在神经元和AD病理之间的关系 杏仁核神经元的化学定义群体。 结构性 内在神经元的基底及其突触关系将是 采用NADPH组织化学进行光镜和电镜分析 以及抗生长抑素（SOM）和神经肽酪氨酸（NPY）的抗血清。 这项研究的结果与广泛的基础和 临床神经科学研究。 杏仁核在大脑中的重要性 边缘回路和该回路的中断导致衰弱 记忆力注意力和情感方面的缺陷 这些研究的结果将 提供定性和定量信息， 理解突触水平的结构-功能关系， 正常老年人，以及神经系统疾病， 癫痫、老年痴呆症和帕金森病。

The overall goal of this research proposal is to elucidate morphologic relations and alterations of neurons in human amygdala obtained at autopsy from normal aged individuals and those afflicted with Alzheimer's disease (AD). The amygdala occupies a strategic position in the circuitry of the limbic system, maintaining connections between cortical association areas and visceral-associated nuclei located subcortically, and undergoes severe pathologic alterations in AD. The first aim is to determine whether pathological alterations resulting from AD have predilection for specific amygdaloid nuclei. Initial morphometric analyses seek to determine whether amygdaloid atrophy in AD correlates with decreased neuronal-packing density, reduced neuronal size or neuron loss. The topographic distribution of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) will be mapped using thioflavin S to test the hypothesis that certain amygdaloid nuclei are selectively vulnerable in AD. Amygdaloid nuclei with severe, intermediate and negligible levels of pathology will be selectively studied at the ultrastructural level to ascertain synaptic relations between normal and pathologically altered structures, and to determine whether alterations in synaptic length and synaptic density correlate with AD. The second aim is to determine the relationship between NFTs in cortical and amygdaloid projection neurons, and NPs in several of their respective terminal fields. Data from morphometric analyses of temporal cortical areas, including hippocampal formation and subcortical nuclei connectionally related to the amygdala will be used to test for a transneuronal effect in the pathogenesis of AD. The third aim entails using experimental neuroanatomical techniques to determine the relationships between intrinsic neurons and AD pathology in chemically defined populations of amygdaloid neurons. The structural substrate of intrinsic neurons and their synaptic relations will be analyzed with light and electron microscopy using NADPH histochemistry and antisera against somatostatin (SOM) and neuropeptide tyrosine (NPY). The results of this research are relevant to a wide range of basic and clinical neuroscience research. The amygdala figures prominently in limbic circuitry and interruptions of this circuitry cause debilitating deficits in memory, attention and affect. Results of these studies will provide qualitative and quantitative information fundamental to understanding structure-function relationships at the synaptic level in normal aged individuals, as well as in neurological disorders such as epilepsy, Alzheimer's and Parkinson's diseases.