CORE--NEUROPATHOLOGY

核心--神经病理学

• 批准号: 6917752
• 负责人: CHARLES LEE WHITE
• 金额: $ 12.73万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6917752
• 关键词: Alzheimer' s disease; biomedical facility; brain morphology; dementia; histopathology; human tissue; neuropathology; patient oriented research; tissue resource /registry

Neuropathologic evaluation remains the "gold standard" for identifying the cause(s) of dementia. The major responsibilities of this Core are to perform the neuropathologic studies necessary to document the diagnosis of Alzheimer disease (AD) and/or other pathologic entities in all human brain specimens used in research studies proposed by investigators within and outside of the ADC, and to provide clinico-pathologic correlation for ADC Clinical Core patients. Therefore, in Specific Aim 1, we will maintain a human brain tissue bank whose mail functions will be: 1) to collect, prepare, evaluate (including ApoE genotyping), catalog, store, and distribute well-characterized postmortem brain tissue and other samples (including postmortem DNA) from deceased demented and control subjects for use in research; 2) to report qualitative and quantitative diagnostic information to physicians, families, and researchers; 3) to work with the Clinical Core to provide clinico-pathologic correlation; and 4) to regularly update the central ADC and National Alzheimer Coordinating Center (NACC) databases with diagnostic and other related information on autopsied and biopsied subjects. In order to enhance the neuropathologic characterization of brain tissue accessioned through this Core, in Specific Aim 2, we will also focus on providing extensive quantitative neuropathologic evaluations for correlation with clinical and research data. The specific analyses to be performed will include: 1) ongoing quantification of synapse density (by measuring concentration of synaptophysin) in postmortem neocortex using an enzyme-linked immunosorbant assay (ELISA) the we developed; 2) quantification of neocortical neuritic dystrophy in sections immunostained for tau and alpha-synuclein using optimized, highly sensitive and specific immunostaining techniques and computer assisted light microscopic image analysis; and 3) quantification of brain microvascular alterations, including blood vessel amyloid deposition and arteriosclerosis/lipohyalnosis and cerebral white matter density, using immunostaining and computer assisted light microscopic image analysis. The thorough neuropathologic characterization of brain tissue as proposed in this Core, utilizing a novel combination of state-of-the-art staining techniques and quantitative analyses, will provide the highest level of diagnostic certainty attainable, and ensure that appropriate tissues are used for research projects.

神经病理评估仍然是识别痴呆症原因的“黄金标准”。该核心的主要责任是进行记录ADC内外研究人员所提出的所有人脑标本中使用的所有人脑标本中的阿尔茨海默氏病（AD）和/或其他病理学实体所必需的神经病理学研究，并为ADC临床核心核心核心核心患者提供了临床病理相关性。因此，在特定目标1中，我们将维护一个人类脑组织，其邮件功能将为：1） 收集，准备，评估（包括APOE基因分型），目录，存储和分布良好的术后脑组织和其他样品（包括死亡后DNA），可用于研究中的痴呆症和控制受试者； 2）向医师，家庭和研究人员报告定性和定量诊断信息； 3）与临床核心合作以提供临床病理相关性； 4）定期更新中央ADC和国家阿尔茨海默氏症协调中心（NACC）数据库，其中包含诊断和其他相关信息，上面有关尸检和活检主题。为了增强通过该核心的脑组织的神经病理表征，在特定的目标2中，我们还将专注于提供广泛的定量神经病理学评估，以与临床和研究数据相关。要进行的特定分析将包括：1）我们开发的酶 - 链接的免疫吸收测定法（ELISA）持续量化突触密度（通过测量突触素的浓度）持续定量。 2）使用优化的，高度敏感和特定的免疫染色技术以及计算机辅助的光，对tau和α-突触核蛋白免疫染色的切片中的新皮质神经营养不良量定量 微观图像分析； 3）使用免疫染色和计算机辅助光显微镜图像分析，定量脑微血管改变，包括血管淀粉样蛋白沉积和动脉粥样硬化/脂肪硬膜病和脑白质密度。 该核心中提出的脑组织的彻底神经病理表征，利用最先进的染色技术和定量分析的新型组合将提供最高水平的诊断确定性，并确保将适当的组织用于研究项目。