CORE--NEUROPATHOLOGY

核心--神经病理学

• 批准号: 7458887
• 负责人: HARRY V. VINTERS
• 金额: $ 32.64万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7458887
• 关键词: Alzheimer' s Disease; Amyloid; Antibodies; Arterioloscleroses; Autopsy; Blood Vessels; Brain; Brodmann' s area; Cerebral Atheroscleroses; Cerebral cortex; Cerebrovascular Disorders; Clinical; Correlative Study; Data; Databases; Dementia; Depth; Diabetic Angiopathies; Diagnosis; Evaluation; Fiber; Future; Gene Expression; Goals; Gray unit of radiation dose; Harvest; Heterogeneity; Hippocampus (Brain); Image; Individual; Lesion; Lewy Bodies; Measures; Methodology; Methods; Modems; Molecular; Neocortex; Neurofibrillary Tangles; Neuropsychological Tests; Outcome Measure; Patients; Pattern; Relative (related person); Research; Resources; Role; Score; Senile Plaques; Severities; Specimen; Techniques; Tissue Microarray; Tissues; Variant; Vascular Dementia; Vascular Diseases; brain tissue; central gray matter; interest; ischemic lesion; neuroimaging; neuropathology; neuropsychological; programs; white matter; white matter injury

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.

该计划项目提供了一个独特的机会来研究，使用现代神经病理学技术，缺血性血管性痴呆（IVD）患者的大脑，这些患者已被详细的临床，神经心理学和复杂的神经影像学检查纵向跟踪多年。尸检时将采用严格的标准化神经病理学评估对这些个体的脑组织进行检查，重点是识别脑动脉粥样硬化和微血管疾病（尤其是动脉硬化/小动脉硬化）的模式 以及它们在产生局灶性脑损伤、大脑皮层和白色物质内的局部缺血性变化以及“阿尔茨海默病”的严重程度中的作用。将获得研究的每个大脑的脑血管疾病和缺血性实质病变（CVD/IVD路径评分）的定量测量结果。将采用形态学（包括免疫组织化学）方法评价可能反映非梗死性皮质/白色物质损伤的脑内参数。这些考试的数据将用于制定一个 复杂的神经病理学数据库，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随访患者的一个“结局”指标。我们还将使用组织微阵列（TMAs）或组织芯片的新方法来研究给定大脑中病变的神经解剖异质性，以及所检查的不同大脑之间的差异，并将其作为阿尔茨海默病中心的资源， 实质性与血管性痴呆的神经病理学变化模式。