Precision Neuropathology Core

摘要-精密神经病理学核心 精密神经病理(NP)核心已成为UW ADRC的宝贵和常用资源 以支持其描述和了解阿尔茨海默病及其相关疾病的异质性的愿景 痴呆(ADRD)。NP核心促进了创新方法的发展，以评估 ADRD的神经病理，这对于更准确地测量神经病理变化是必不可少的。我们在此基础上 这项提案的创新传统是通过应用新的、高度定量的多重免疫分析 在NP Core中开发，用于测量神经病理，结合更好的收集和 存储组织用于最先进的应用，包括单细胞分子图谱、扩展病理 通过结构和功能成像进行采样，每个大脑在体外MRI引导下进行病理采样， 和3D图像重建，以及对大体和微观样本的定量分析，使我们能够 深入表征ADRD异质性的结构衬底。我们结合了这一全面的分析 由各自领域的专家组成的具有细胞类型和干细胞成分的人脑 致力于为与ADRD相关的机制研究提供支持，同时支持 ADRC以及地方和国家的研究。因此，我们的目标反映了我们致力于整合传统 卓越的诊断能力和广泛的组织和数据共享，并通过放射学知情的广泛采样 以及一组高度定量的、分子特异性的组织，并在电子技术中精确测量 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， (2)根据最新准则提供诊断专门知识；(3)开发创新办法；(4) 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 支持ADRC核心、发展项目以及地方和国家研究。我们所有的研究活动 致力于提高来自认知健康的组织和体液捐赠的研究价值 在确保适当保障的同时，为个人和ADRD谱系沿线的人提供保护。

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.