CORE--NEUROPATHOLOGY

神经病理学核心(NPC)的目标将是使用神经心理学评估和神经成像对临床随访的研究患者的尸检获得的大脑提供标准化的神经病理评估，以表征缺血性血管病变和实质退行性变化(例如阿尔茨海默病)对特定患者痴呆的相对贡献。具体的神经病理参数(见下文)将在缺血性血管性痴呆(IVD)、阿尔茨海默病和对照组患者之间进行比较。我们将通过评估(A)程度和(B)可能导致痴呆的脑软化病变的分布来操作IVD的神经病理基础的评估。将维持一个神经病理数据库，并在必要时向其他项目提供数据，以促进死前(包括代谢)成像研究和死后脑发现之间的相关性，重点是确定腔隙梗死的放射特征，以及它们可能通过逆行和跨突触退化机制对皮质完整性的影响。将被详细评估的IVD)将包括白质(轴突、髓鞘)内的变化以及投射到白质的神经元的密度和大小(结合项目#3)。利用免疫组织化学和定量形态计量学方法，评估IVD的可能神经病理基础包括：(A)以葡萄糖转运体免疫反应的毛细血管和肥大的小动脉的异常分布/密度为特征的微血管损害，(B)微血管病变对邻近脑实质的继发性损害(例如葡萄糖转运体免疫反应的毛细血管的轴突/髓鞘密度和肥大的小动脉)，(B)微血管病变对邻近脑实质的继发性损害(例如轴突/髓鞘密度，APP表达)和炎症/反应细胞(小胶质细胞，星形胶质细胞)，以及(C)海马区的正常损害。神经病理学数据将被提供给研究项目，所有临床/实验数据将在这些项目中根据神经病理学结果进行重新评估。其预期结果是基于多模式、功能和神经解剖学的患者评估，提供IVD最详细的可用病理生理学表现。

The goals of the Neuropathology Core (NPC) will be to provide standardize neuropathologic assessment of brains obtained at autopsy from study patients who have been followed clinically, using neuropsychological evaluations and neuroimaging, in order to characterize the relative contributions of ischemic vascular lesions and parenchymal degenerative changes (e.g. of Alzheimer disease) to a given patient's dementia. Comparisons of specific neuropathologic parameters (see below) will be made among ischemic vascular dementia (IVD), Alzheimer and control patients. We will operationalize assessment of neuropathologic substrates of IVD by evaluating both (a) extent, and (b) distribution of encephalomalacic lesions that may contribute to dementia. A neuropathologic data base will be maintained and data will be provided to other projects as necessary to facilitate correlations between pre- mortem (including metabolic) imaging studies and postmortem brain findings, with an emphasis on defining radiographic features on lacunar infarcts, and their possible impact upon cortical integrity by mechanisms of retrograde and trans-synaptic degeneration. Possible neuroanatomical correlates of ischemic vascular dementia )IVD) to be evaluated in detail will include changes within white matter (axons, myelin sheaths) and densities and sizes of neurons projecting into the white matter (in conjugation with Project #3). Possible neuropathologic substrates of IVD to be evaluated, using immunohistochemistry and quantitative morphometry, will include (a) microvascular lesions characterized as abnormal distributions/densities of glucose transporter-immunoreactive capillaries, and hypertrophic arterioles, (b) secondary injurious effects of microvasculopathy upon adjacent brain parenchyma (e.g. axon/myeline densities of glucose transporter-immunoreactive capillaries, and hypertrophic arterioles, (b) secondary injurious effects of microvasculopathy upon adjacent brain parenchyma (e.g. axon/myelin densities , APP expression) and inflammatory/reactive cells (microglia, astrocytes), and (c) hippocampal abnormalities indicative of hippocampal sclerosis or scarring. Neuropathologic data will be provided to the investigational projects and all clinical/experimental data will be re- evaluated in these projects in light of neuropathologic outcomes. The intended result is to provide the most detailed available pathophysiologic representation of IVD based upon multi-modality functional and neuroanatomical patient evaluation.