CORE--NEUROPATHOLOGY

神经病理学核心（NPC）的目标是对临床随访的研究患者的尸检结果进行标准化的脑神经病理学评估，使用神经心理学评估和神经影像学，以表征缺血性血管病变和实质退行性改变（如阿尔茨海默病）对特定患者痴呆的相对贡献。将在缺血性血管性痴呆（IVD）、阿尔茨海默病（Alzheimer）和对照组患者之间进行特定神经病理参数的比较（见下文）。我们将通过评估(a)可能导致痴呆的脑瘤性病变的范围和(b)分布，对IVD的神经病理基础进行操作性评估。将维持一个神经病理学数据库，并根据需要向其他项目提供数据，以促进死前（包括代谢）成像研究与死后脑发现之间的相关性，重点是确定腔隙性梗死的放射学特征，以及它们通过逆行和跨突触变性机制对皮质完整性的可能影响。要详细评估的缺血性血管性痴呆（IVD）可能的神经解剖学相关性将包括白质（轴突、髓鞘）内的变化以及投射到白质中的神经元的密度和大小（与项目#3结合）。使用免疫组织化学和定量形态学来评估IVD可能的神经病理底物，将包括(a)微血管病变，其特征为葡萄糖转运免疫反应毛细血管和肥厚小动脉的异常分布/密度，(b)微血管病变对邻近脑实质的继发性损伤作用（例如葡萄糖转运免疫反应毛细血管的轴突/髓系密度，肥厚小动脉）。(b)微血管病变对邻近脑实质（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）的继发性损伤作用，以及(c)表明海马硬化或瘢痕形成的海马异常。神经病理学数据将提供给研究项目，所有临床/实验数据将根据神经病理学结果在这些项目中重新评估。预期的结果是根据多模态功能和神经解剖患者评估，提供最详细的IVD病理生理表征。

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.