Neuropathology Core

神经病理学核心

• 批准号: 10407938
• 负责人: DENNIS WILLIAM DICKSON
• 金额: $ 54.68万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10407938
• 关键词: Address; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Animal Model; Animals; Apolipoprotein E; Astrocytes; Autopsy; Biochemical; Bioinformatics; Biological Assay; Biology; Biometry; Blood Vessels; Brain; Brain region; Cell model; Cells; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Clinic; Collaborations; Collection; Communities; Complement; Confocal Microscopy; Data; Deposition; Disease; Enzyme-Linked Immunosorbent Assay; Florida; Freezing; Genetic; Genotype; Goals; Histologic; Human; Immunoassay; Immunohistochemistry; Individual; Inflammatory; Knowledge; Lewy Bodies; Lewy Body Disease; Link; Lipoproteins; Measurement; Measures; Methods; Microglia; Nerve Degeneration; Neurons; Outcome; Pathologic; Pathology; Pathway interactions; Patients; Phenotype; Principal Investigator; Process; Protein Isoforms; Proteomics; Research; Research Personnel; Resources; Risk; Role; Sampling; Senile Plaques; Services; Severities; Site; Source; Standardization; Synapses; Tauopathies; Testing; Tissues; United States; Universities; Validation; Washington; Work; age related; alpha synuclein; biophysical analysis; biophysical properties; brain tissue; cell type; cerebrovascular; cohort; comorbidity; cytokine; data management; density; digital; digital pathology; gene product; genetic association; genomic locus; glial activation; human model; innovation; mind control; multi-ethnic; multiple omics; neuroinflammation; neuropathology; normal aging; novel; particle; protein TDP-43; response; sex; tau Proteins; tool; transcriptomics; web portal

PROJECT SUMMARY (APOE U19 Core C: Neuropathology Core) The Neuropathology Core (Core C) supports the ultimate goal of understanding the ApoE Cascade Hypothesis by providing neuropathologic support to the projects and cores of the U19. A major focus of Core C efforts is on assessing the impact of APOE genotype on comorbid pathologies in Alzheimer’s disease and other aging- related conditions. The brain bank at Mayo Clinic in Jacksonville (MCJ) will be the major source of postmortem brain samples used in the cores and projects, supplemented by samples from the brain bank at Washington University in St. Louis (WUSTL). Brain samples will be crucial to analyses of biochemical and biophysical properties of brain apoE-lipoprotein particles performed by Core B and for the proteomic and transcriptomic studies performed by Core F. Core C will characterize tissues provided to the investigators in the U19 using immunoassays that measure levels of apoE, Aβ, tau, synaptic markers, glial activation markers, inflammatory cytokines, as well as markers of vascular integrity, and other aging and AD-related molecules. The role of comorbid or mixed pathology will be assessed in AD and control brains by assessing quantitative measures of amyloid deposits, amyloid angiopathy, neuronal and glial tau pathologies, α-synuclein pathology and TDP-43 pathology. Core C will work closely with Project 5 investigators to investigate neuropathologic phenotypes associated with novel genetic modifiers of APOE risk, and it will develop novel assays, as needed, to study the gene products implicated in Project 5 genetic association studies. It will assist Project 2 investigators in histologic and neuropathologic assessment of astrocytic and microglial response to Aβ-induced local damage, Aβ-induced tau spreading, and tau-mediated neurodegeneration in animal models. Finally, Core C will assist investigators in Projects 3 and 4 with digital pathologic method to systematically assess markers of glial activation and other neuropathologic measures in animal and cellular models. Core C supports individual components of the U19 by providing neuropathology services and resources to address gaps in knowledge with the ultimate goal of testing the ApoE Cascade Hypothesis. Core C will use cutting edge methods, such as digital pathology and confocal microscopy, to address critical knowledge gaps in our collective efforts to understand why APOE genotype has a profound effect on risk for AD and other ageing-related conditions. In addition, Core C will share valuable resources (brain tissues and relevant data) with the Multi-Omics, Bioinformatics, Biostatistics, and Data Management Core (Cores F and G), as well as the general scientific community via U19 web portal (www.EPAAD.org).

项目总结(APOE U19核心C：神经病理学核心) 神经病理学核心(核心C)支持理解载脂蛋白E级联假说的最终目标 通过为U19的项目和核心提供神经病理支持。Core C工作的一个主要重点是 关于评估载脂蛋白E基因对阿尔茨海默病和其他衰老的共病病理的影响 相关条件。杰克逊维尔梅奥诊所的脑库将是尸检的主要来源 核心和项目中使用的大脑样本，以及来自华盛顿脑库的样本 圣路易斯大学(WUSTL)。大脑样本将是生化和生物物理分析的关键 核心B执行的脑载脂蛋白颗粒的性质及其蛋白质组学和转录组学研究 由Core F.Core C执行的研究将使用以下方法表征提供给U19调查人员的组织 检测载脂蛋白E、Aβ、tau、突触标志物、神经胶质细胞活化标志物、炎症的免疫分析 细胞因子，以及血管完整性的标志，以及其他与衰老和AD相关的分子。的作用 阿尔茨海默病患者和对照大脑将通过评估定量测量的 淀粉样蛋白沉积、淀粉样血管病变、神经元和神经胶质tau病理、α-突触核蛋白病理和Tdp-43 病理学。CORE C将与项目5调查人员密切合作，调查神经病理表型 与APOE风险的新遗传修饰物相关，并将根据需要开发新的分析方法来研究 项目5基因关联研究中涉及的基因产品。它将协助项目2的调查人员 星形胶质细胞和小胶质细胞对β诱导的局部损伤反应的组织学和神经病理学评价， β诱导的tau扩散，以及tau介导的动物模型中的神经变性。最后，Core C将协助 项目3和项目4的研究人员使用数字病理学方法系统地评估神经胶质细胞的标记物 在动物和细胞模型中的激活和其他神经病理测量。核心C支持个人 U19的组成部分，通过提供神经病理学服务和资源来解决知识差距 最终目的是检验ApoE级联假说。核心C将使用尖端方法，例如 数字病理学和共聚焦显微镜，以解决我们集体努力中的关键知识缺口 了解为什么载脂蛋白E基因对AD和其他与衰老相关的疾病的风险有深远的影响。在……里面 此外，Core C将与MultiOmics共享宝贵的资源(脑组织和相关数据)， 生物信息学、生物统计学和数据管理核心(核心F和G)，以及一般科学 通过U19门户网站(www.EPAAD.org)创建社区。