Neuropathology Core

神经病理学核心项目摘要/摘要 人脑组织在ADRD研究中的重要性怎么强调都不为过，两者都是值得探索的资源 并定义了新的分子途径，以及希望验证的动物研究人员的关键资源 他们在人体组织中的发现。NIA最近发起的AMP-AD倡议是对 人类脑组织在定义疾病相关途径中的重要性，并导致了许多 这些出版物增加了我们对AD发病机制的不断发展的理解。哥伦比亚大学ADRC 神经病理学(NP)Core长期以来一直服务于更广泛的ADRD研究界对Well 描述了人脑组织，我们将在这一新的P30应用下继续这一使命。酋长 NP核心的职能是提供最先进的诊断服务，并收集、维护和分发 为哥伦比亚大学和世界各地的研究人员精心准备了大脑样本。NP Core还拥有 培养和教育下一代神经退行性疾病研究人员和大脑的责任 银行家。最后，NP核心将有助于对作为科学焦点的三条途径的调查 此应用程序的。 关于组织储存和分发，NP Core有一套完善的程序，用于接收和分发 银行大脑，我们将在这个新的P30应用程序中继续这个协议。捐赠者死亡时，一半 大脑浸泡在福尔马林中，保存下来进行彻底的神经病理学评估，对侧半脑 在新鲜状态下广泛解剖并加工，可生产多达150块和粉碎等分的 薄壁组织。我们的样品是条形码和电子跟踪的，这有助于组织样品， 安全地维护它们，并最终加快研究样本的选择。在教育方面， NP Core有着培养下一代神经科学家和脑银行家的悠久传统， 通过每周切脑，每月临床病理会议，并定期主持访问 全世界的神经学家(自2001年以来，我们的方法论已经完全或部分建立在8 其他学术站点)。最后，我们将使用NP核心的资源来通报与AD相关的三个 生物途径。具体地说，我们将使用单核rna-seq来问以下问题：1)什么 细胞类型表达与三条通路(即TREM2、APOE、SORL1)有关的三个已建立的基因。 2)表达这三个基因的细胞类型是否存在区域差异？3)这三个基因是否表达 在连续的布拉克阶段中的模式变化？

NEUROPATHOLOGY CORE PROJECT SUMMARY/ABSTRACT The importance of human brain tissue in ADRD research cannot be overstated, both as a resource to explore and define novel molecular pathways, as well as a critical resource for animal researchers who wish to validate their findings in human tissue. The AMP-AD initiative recently launched by NIA is further validation of the importance of human brain tissue in defining disease-relevant pathways, and has resulted in numerous publications that have added to our evolving understanding of AD pathogenesis. The Columbia University ADRC Neuropathology (NP) Core has a long history of serving the wider ADRD research community’s need for well characterized human brain tissue, and we will continue this mission under this new P30 application. The chief function of the NP Core is to provide state-of-the-art diagnostic services, and to collect, maintain, and distribute optimally prepared brain samples to researchers at Columbia and throughout the world. The NP Core also has a responsibility to train and educate the next generation of neurodegenerative disease researchers and brain bankers. Finally, the NP Core will contribute to the investigation of the three pathways that are the scientific focus of this application. With regards to tissue banking and distribution, the NP Core has a well-established procedure for receiving and banking brains, and we will continue this protocol for this new P30 application. Upon death of a donor, one half brain is immersed in formalin and kept for thorough neuropathological evaluation, and the contralateral half is extensively dissected at the fresh state and processed to yield up to 150 blocks and pulverized aliquots of parenchyma. Our samples are barcoded and electronically tracked, which aids in organizing the samples, maintaining them safely, and ultimately speeds the selection of samples for research. With regards to education, the NP Core has a long-standing tradition of educating the next generation of neuroscientists and brain bankers, through weekly brain cutting, monthly clinicopathological conferences, and periodic hosting of visiting neuroscientists throughout the world (since 2001, our methodology has been fully or partially instituted at eight other academic sites). Finally, we will use the resources of the NP core to inform on the three AD-associated biological pathways. Specifically, we will use single-nucleus RNA-seq to ask the following questions: 1) What cell types express the three established genes that relate to the three pathways (i.e. TREM2, APOE, SORL1)?; 2) Is there regional variation in the cell types that express these three genes?, and 3) Does this expression pattern change during successive Braak stages?