Precision Neuropathology Core

精准神经病理学核心

• 批准号: 10661536
• 负责人: CHRISTOPHER DIRK KEENE
• 金额: $ 57.28万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10661536
• 关键词: Abbreviations; Acceleration; Adult; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease related dementia; Autopsy; Biological; Biological Assay; Biological Markers; Body Fluids; Brain; Brain imaging; Brain region; Cells; Cellular Structures; Clinical; Cognitive; Consensus; Data; Dementia; Development; Diagnostic; Ensure; Equipment and supply inventories; Evaluation; Experimental Models; Family; Fostering; Functional Imaging; Funding; Future; Genetic; Goals; Guidelines; Heterogeneity; Human; Image; Immunoassay; Individual; Infrastructure; Investments; Knowledge; Leadership; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medicine; Methods; Microscopic; Molecular; Molecular Profiling; Names; Nerve Degeneration; Pathologic; Pathologic Processes; Pathology; Peptides; Phase; Policies; Positioning Attribute; Process; Productivity; Psychometrics; Publications; Recording of previous events; Reporting; Research; Research Activity; Research Personnel; Research Subjects; Research Support; Resources; Sampling; Specimen; Stem Cell Research; Supporting Cell; Therapeutic; Three-Dimensional Image; Tissues; Training; United States National Institutes of Health; Vision; biobank; biological heterogeneity; brain research; brain tissue; cell type; cohort; data management; data quality; data sharing; education research; image reconstruction; improved; in silico; innovation; neuroimaging; neuroinflammation; neuropathology; neurotoxicity; next generation; non-demented; novel; outreach; radiological imaging; recruit; repository; screening; statistics; stem cells; structural imaging; virtual

Abstract - Precision Neuropathology Core The Precision Neuropathology (NP) Core has been a valuable and frequently utilized resource for UW ADRC in support of its vision of characterizing and understanding heterogeneity of Alzheimer's disease and related dementias (ADRD). The NP Core has fostered development of innovative approaches to assess neuropathology of ADRD, which are essential to more precisely measure neuropathologic change. We build on this tradition of innovation in this proposal by applying novel, highly quantitative multiplexed immunoassays developed in the NP Core to measure neuropathology that, combined with better methods of collecting and storing tissue for state-of-the-art applications including single cell molecular profiling, expanded pathological sampling informed by structural and functional imaging, ex vivo MRI-guided pathologic sampling in every brain, and 3D image reconstruction, and quantitative analysis in both gross and microscopic samples, enable us to deeply characterize the structural substrate for ADRD heterogeneity. We combine this comprehensive analysis of human brains with a cell types and stem cell component composed of experts in their respective fields who are committed to providing support for ADRD-related mechanistic studies, all while supporting every core of the ADRC and local and national research. Thus, our Aims reflect our commitment to integrate traditional diagnostic excellence and extensive tissue and data sharing with radiographically informed extensive sampling and a battery of highly quantitative, molecularly specific tissue and in silico approaches to precisely measure ADRD neuropathology. Our specific aims are to (i) build a highly accessible repository of brain tissue and fluid, (ii) provide diagnostic expertise according to the latest guidelines, (iii) develop innovative approaches, (iv) provide cell types and stem cell support for ADRD research, and (v) promote durable ADRD research through support of ADRC Cores, development projects, and local and national research. All of our research activities are focused on enhancing the research value of tissue and body fluid donations from cognitively healthy individuals and those along the ADRD spectrum while ensuring proper safeguards.

摘要 - 精准神经病理学核心 精密神经病理学 (NP) 核心一直是华盛顿大学 ADRC 的宝贵且经常使用的资源 支持其描述和理解阿尔茨海默病及相关疾病异质性的愿景 痴呆症（ADRD）。 NP 核心促进了评估创新方法的发展 ADRD 的神经病理学，这对于更精确地测量神经病理变化至关重要。我们建立在 本提案中的创新传统是通过应用新颖的、高度定量的多重免疫测定法 在 NP 核心中开发的用于测量神经病理学的方法，结合更好的收集和分析方法 存储组织用于最先进的应用，包括单细胞分子分析、扩展病理学 通过结构和功能成像、离体 MRI 引导的每个大脑的病理采样提供信息， 和 3D 图像重建以及宏观和微观样本的定量分析使我们能够 深入表征 ADRD 异质性的结构基础。我们结合这个综合分析 具有细胞类型和干细胞成分的人类大脑由各自领域的专家组成 致力于为 ADRD 相关机制研究提供支持，同时支持每个核心 ADRC 以及地方和国家研究。因此，我们的目标反映了我们整合传统传统的承诺 卓越的诊断以及广泛的组织和数据共享以及放射学信息广泛采样 以及一系列高度定量、分子特异性的组织和计算机方法来精确测量 ADRD 神经病理学。我们的具体目标是（i）建立一个高度可访问的脑组织和液体储存库， (ii) 根据最新指南提供诊断专业知识，(iii) 开发创新方法，(iv) 为 ADRD 研究提供细胞类型和干细胞支持，以及 (v) 通过以下方式促进持久的 ADRD 研究 ADRC 核心、开发项目以及地方和国家研究的支持。我们所有的研究活动 致力于提高认知健康者捐赠的组织和体液的研究价值 个人和 ADRD 范围内的人，同时确保适当的保障措施。