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ApoE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学支持。核心C工作的一个主要重点是 评估载脂蛋白E基因型对阿尔茨海默病和其他衰老共病病理的影响- 相关条件。位于杰克逊维尔（MCJ）的马约诊所的脑库将是死后尸检的主要来源。 核心和项目中使用的大脑样本，以及来自华盛顿大脑银行的样本 圣路易斯大学（WUSTL）。大脑样本将是至关重要的生化和生物物理分析 通过Core B进行的脑apoE-脂蛋白颗粒的性质以及蛋白质组学和转录组学 由Core F进行的研究。核心C将使用以下方法表征提供给U19研究者的组织 免疫测定法测量apoE、Aβ、tau、突触标志物、神经胶质活化标志物、炎性 细胞因子，以及血管完整性的标志物，以及其他衰老和AD相关分子。的作用 将通过评估AD和对照脑中的共病或混合病理的定量测量来评估AD和对照脑中的共病或混合病理。 淀粉样蛋白沉积、淀粉样血管病、神经元和神经胶质tau病理、α-突触核蛋白病理和TDP-43 病理核心C将与项目5研究者密切合作，研究神经病理表型 与APOE风险的新型遗传修饰剂相关，它将根据需要开发新的检测方法，以研究APOE风险的基因修饰剂。 与项目5遗传关联研究有关的基因产物。它将协助项目2调查人员 星形胶质细胞和小胶质细胞对Aβ诱导局部损伤反应的组织学和神经病理学评估， 动物模型中Aβ诱导的tau扩散和tau介导的神经变性。最后，核心C将协助 研究者在项目3和4中采用数字病理方法系统地评估胶质细胞标志物， 活化和其他神经病理学测量。核心C支持个人 通过提供神经病理学服务和资源来解决知识差距， 最终目标是测试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差距， 了解为什么APOE基因型对AD和其他衰老相关疾病的风险有深远的影响。在 此外，Core C将与Multi-Omics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）访问社区。