Neuropathology Core

神经病理学核心

基本信息

批准号：
10667443
负责人：
DENNIS WILLIAM DICKSON
金额：
$ 54.48万
依托单位：
MAYO CLINIC JACKSONVILLE
依托单位国家：
美国
项目类别：
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/10667443
关键词：
Address Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease patient Alzheimer&apos 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 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 apolipoprotein E-4 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

项目摘要

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).

项目摘要（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为 U19 的项目和核心提供神经病理学支持核心 C 工作的主要重点是。评估 APOE 基因型对阿尔茨海默病和其他衰老疾病的共病病理的影响杰克逊维尔梅奥诊所 (MCJ) 的脑库将成为尸检的主要来源。核心和项目中使用的大脑样本，并以华盛顿脑库的样本为补充圣路易斯大学 (WUSTL) 的大脑样本对于生物化学和生物物理分析至关重要。 Core B 执行的脑 apoE-脂蛋白颗粒的特性以及蛋白质组学和转录组学由 Core F 进行的研究。Core C 将使用 U19 来表征提供给研究人员的组织测量 apoE、Aβ、tau、突触标记物、神经胶质激活标记物、炎症水平的免疫测定细胞因子以及血管完整性标记物以及其他衰老和 AD 相关分子的作用。将通过评估 AD 和对照大脑的定量测量来评估共病或混合病理学淀粉样蛋白沉积、淀粉样血管病、神经元和神经胶质 tau 蛋白病理学、α-突触核蛋白病理学和 TDP-43 Core C 将与 Project 5 研究人员密切合作，研究神经病理表型。与 APOE 风险的新型基因修饰剂相关，并且将根据需要开发新的方法来研究分析项目 5 遗传关联研究中涉及的基因产物将协助项目 2 的研究人员进行。星形胶质细胞和小胶质细胞对 Aβ 诱导的局部损伤反应的组织学和神经病理学评估，最后，Core C 将有助于动物模型中 Aβ 诱导的 tau 扩散和 tau 介导的神经变性。项目3和4的研究人员采用数字病理方法系统评估神经胶质标记物动物和细胞模型中的激活和其他神经病理学测量 Core C 支持个体。 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标是测试 ApoE 级联假设，Core 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产生深远影响。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），以及一般科学知识通过 U19 门户网站 (www.EPAAD.org) 建立社区。