CORE--NEUROPATHOLOGY

神经病理学核心（NPC）的目标是使用神经心理学评价和神经影像学，对临床随访的研究患者尸检时获得的大脑进行标准化神经病理学评估，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）对给定患者痴呆的相对贡献。将在缺血性血管性痴呆（IVD）、阿尔茨海默病和对照患者中比较特定的神经病理学参数（见下文）。我们将通过评估可能导致痴呆的脑软化病变的（a）程度和（B）分布，对IVD的神经病理学基质进行操作性评估。将维护神经病理学数据库，并根据需要向其他项目提供数据，以促进尸检前（包括代谢）成像研究与尸检脑结果之间的相关性，重点是定义腔隙性梗死的放射学特征，以及其通过逆行和跨突触变性机制对皮质完整性的可能影响。待详细评价的缺血性血管性痴呆（IVD）的可能神经解剖学相关性将包括白色物质（轴突、髓鞘）内的变化以及投射到白色物质中的神经元的密度和大小（结合项目#3）。使用免疫组织化学和定量形态测定法评价的IVD可能的神经病理学基质包括（a）微血管病变，其特征为葡萄糖转运蛋白免疫反应性毛细血管和肥大小动脉的异常分布/密度，（B）微血管病变对邻近脑实质的继发性损伤作用（例如葡萄糖转运蛋白免疫反应性毛细血管和肥大小动脉的轴突/髓鞘密度，（B）微血管病变对邻近脑实质的继发性损伤作用（c）指示海马硬化或瘢痕形成的海马异常。将向研究项目提供神经病理学数据，并根据神经病理学结局在这些项目中重新评价所有临床/实验数据。预期结果是根据多模态功能和神经解剖学患者评价，提供IVD最详细的可用病理生理学表示。

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.