Neuropathology Core

神经病理学核心项目总结/摘要 人脑组织在ADRD研究中的重要性怎么强调都不过分， 并定义新的分子途径，以及动物研究人员希望验证的关键资源 他们在人体组织中的发现NIA最近发起的AMP-AD倡议进一步验证了 人类大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发病机制的理解。哥伦比亚大学ADRC 神经病理学（NP）核心有着悠久的历史，服务于更广泛的ADRD研究社区的需要，以及 我们将在这个新的P30应用程序下继续这项使命。首席 NP Core的功能是提供最先进的诊断服务，并收集、维护和分发 最佳制备的大脑样本提供给哥伦比亚和世界各地的研究人员。NP Core还具有 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核心将有助于调查的三个途径，这是科学的重点 这个应用程序。 关于组织库和分配，NP Core有一个完善的接收和分配程序， 银行的大脑，我们将继续这个新的P30应用程序的协议。捐赠者死亡后， 将大脑浸入福尔马林中，并保存以进行彻底的神经病理学评估， 在新鲜状态下广泛解剖，并加工以产生多达150个块和粉碎的等分试样， 薄壁组织我们的样本都有条形码和电子跟踪，这有助于组织样本， 安全地维护它们，并最终加快研究样本的选择。关于教育， NP Core有着教育下一代神经科学家和大脑银行家的悠久传统， 通过每周的脑切割，每月的临床病理学会议，并定期举办访问 世界各地的神经科学家（自2001年以来，我们的方法已经完全或部分建立在八个 其他学术网站）。最后，我们将使用NP核心的资源来告知与AD相关的三个 生物途径。具体来说，我们将使用单核RNA-seq提出以下问题：1）什么 细胞类型表达与三种途径相关的三种已建立的基因（即TREM 2、APOE、SORL 1）; 2)表达这三种基因的细胞类型是否存在区域差异？（3）这个表达式 在连续的布拉克阶段的模式变化？

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?