CORE--NEUROPATHOLOGY

该计划项目提供了一个独特的机会，利用现代神经病理学技术研究缺血性血管性痴呆(IVD)患者的大脑，这些患者经过多年的纵向跟踪，进行了详细的临床、神经心理学和复杂的神经成像检查。这些人的脑组织将在尸检时使用严格、标准化的神经病理评估进行检查，重点是识别脑动脉粥样硬化和微血管疾病的模式(特别是动脉/动脉硬化)。 以及它们在造成局灶性脑损伤、大脑皮层和白质的局部缺血性变化以及“阿尔茨海默化”严重程度方面的作用。脑血管疾病和缺血性实质损害的定量测量(CVD/IVD-Path评分)将为每个被研究的大脑获得。将使用包括免疫组织化学在内的形态学方法评估可能反映非梗死性皮质/白质损伤的脑内参数。这些检查的数据将被用来制定一个 先进的神经病理数据库，其内容将提供给PPG内的其他核心和调查项目，以优化相关数据，使用尸检结果作为纵向跟踪患者的一种“结果”衡量标准。我们还将使用组织微阵列(TMA)或组织芯片的新方法来研究给定大脑中病变的神经解剖学异质性，以及不同被检查大脑之间的差异，并将此作为资源提供给阿尔茨海默病中心进行对比 实质性痴呆与血管性痴呆的神经病理改变模式。

This program project provides a unique opportunity to study, using modem neuropathologic techniques, the brains of patients with ischemic-vascular dementia (IVD) who have been followed longitudinally over years by detailed clinical, neuropsychological, and sophisticated neuroimaging examinations. Brain tissue from these individuals will be examined at necropsy utilizing rigorous, standardized neuropathologic assessment, with a focus on identifying patterns of cerebral atherosclerosis and microvascular disease (especially arterio-/arteriolosclerosis) and their role in producing focal brain lesions, regional ischemic changes within both cerebral cortex and white matter, as well as the severity of 'Alzheimerization'. Quantitative measures of both cerebrovascular disease and ischemic parenchymal lesions (CVD/IVD-path scores) will be obtained for each brain studied. Evaluation of parameters within brain that may reflect non-infarctive cortical/white matter injury using morphologic, including immunohistochemical, methods will be undertaken. Data from these examinations will be used to develop a sophisticated neuropathologic database, the contents of which will be made available to other Cores and investigative Projects within the PPG, in order to optimize correlative data using autopsy findings as one 'outcome' measure in longitudinally followed patients. We will also use the new methodology of tissue microarrays (TMAs) or tissue chips to study the neuroanatomical heterogeneity of lesions in a given brain, as well as variations among different brains examined, and provide this as a resource to Alzheimer Centers with an interest in contrasting patterns of neuropathologic change in parenchymal vs. vascular dementias.