Precision Neuropathology Core

摘要-精密神经病理学核心 精密神经病理学（NP）核心一直是UW ADRC的宝贵和经常使用的资源 为了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学变化是必不可少的。我们建立在 这一传统的创新，在这项建议中，通过应用新的，高度定量的多重免疫测定， 在NP Core中开发的用于测量神经病理学的方法，结合更好的收集和 存储组织用于最先进的应用，包括单细胞分子谱分析、扩增的病理 通过结构和功能成像进行采样，在每个大脑中进行离体MRI引导的病理采样， 和3D图像重建，以及宏观和微观样品的定量分析，使我们能够 深入表征ADRD异质性的结构基质。我们将联合收割机的综合分析 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ADRD相关机制研究提供支持，同时支持每一个核心的 ADRC和地方和国家研究。因此，我们的目标反映了我们的承诺， 卓越的诊断和广泛的组织和数据共享与放射学知情的广泛采样 以及一系列高定量、分子特异性组织和计算机模拟方法， 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库， (ii)根据最新准则提供诊断专门知识，㈢制定创新办法，㈣ 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，开发项目以及地方和国家研究。我们所有的研究活动 专注于提高认知健康的组织和体液捐赠的研究价值， 个人和那些沿着ADRD谱，同时确保适当的保障措施。

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.