Precision Neuropathology Core

精准神经病理学核心

• 批准号: 10171545
• 负责人: CHRISTOPHER DIRK KEENE
• 金额: $ 46.98万
• 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/10171545
• 关键词: Abbreviations; 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 Data; Cognitive; Consensus; Data; Dementia; Development; Diagnostic; Diagnostic radiologic examination; Ensure; Equipment and supply inventories; Evaluation; Experimental Models; Family; Fostering; Functional Imaging; Funding; Future; Goals; Guidelines; Heterogeneity; Human; Image; Immunoassay; Individual; Infrastructure; Investments; Knowledge; Leadership; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medical Genetics; 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; Structure; Supporting Cell; Therapeutic; Three-Dimensional Image; Time; 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; imaging biomarker; improved; in silico; innovation; neuroimaging; neuroinflammation; neuropathology; neurotoxicity; next generation; non-demented; novel; outreach; recruit; repository; screening; statistics; stem cells; 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 - 精确神经病理学核心 精确神经病理学（NP）核心是UW ADRC的宝贵且经常使用的资源 支持其表征和理解阿尔茨海默氏病的异质性及其相关的异质性 痴呆症（ADRD）。 NP核心促进了创新方法的发展 ADRD的神经病理学，这对于更精确地衡量神经病理学的变化至关重要。我们基础 在本提案中，这种创新传统通过应用小说，高定量的多重免疫测定 在NP核心中开发，以衡量神经病理学，结合更好的收集方法和 存储用于最新应用的组织，包括单细胞分子分析，扩展的病理学 通过结构和功能成像，在每个大脑中进行的MRI引导的病理学采样，以 和3D图像重建以及总体和微观样本中的定​​量分析，使我们能够 深层表征了ADRD异质性的结构底物。我们结合了这种全面的分析 具有细胞类型和干细胞成分的人类大脑的组成 致力于为ADRD相关的机械研究提供支持，同时支持的每个核心 ADRC以及本地和国家研究。因此，我们的目标反映了我们对整合传统的承诺 诊断卓越和广泛的组织和数据共享以及射线照相知情的广泛抽样 以及高度定量的，分子特异性组织以及精确度量的计算机方法 ADRD神经病理学。我们的具体目的是（i）建立一个高度可访问的脑组织和流体的存储库， （ii）根据最新指南（iii）开发创新方法，（iv）提供诊断专业知识。 为ADRD研究提供细胞类型和干细胞支持，（v）通过 支持ADRC核心，开发项目以及本地和国家研究。我们所有的研究活动 专注于增强认知健康的组织和体液捐赠的研究价值 在确保适当的保障措施的同时，个人和沿着Adrd频谱的人。