University of Kansas Alzheimers Disease Center P30 Neuropathology supplement

项目摘要 本补编要求提供一年的资金，以支助与联合国大学有关的意外费用。 堪萨斯阿尔茨海默病研究中心（KU ADRC）神经病理学（NP）核心。 神经病理学核心与其他ADRC核心合作，提供关键的KU ADRC基础设施 （图1）。神经病理学的核心功能是必不可少的中心的使命和科学主题1） 维护尸检程序和脑库; 2）提供神经病理学诊断，咨询， 对研究者和受训者进行培训; 3）获得硬脑膜和皮肤活检，以获得诱导多能干细胞 （IPSC）系;和4）提供脑组织用于通过生物标志物核心进行线粒体DNA（mtDNA）测序。 NP核心不断升级其地位，以适应该领域的诊断进展，并根据 批准和接受新的指导方针、知识和最先进的技术。此外，核心还 参与产生这些进步的重要辩论。 请求NP核心支持的调查人员数量意外增加， 条件限制我们的核心，以创建一个数字图书馆的玻璃载玻片，增加要求死后CSF 标本和不可预测的过时，我们的基本设备被替换，断言这一要求。 我们在最近资助的P30中提议，向计算机提供开放的全切片扫描图像库， 科学家和其他研究人员使用病理学部门的扫描仪。但由于 由于部门对肿瘤和其他病理学标本的需求不断增加，我们无法 由于目前的扫描仪速度缓慢，部门无法分配所需的适当时间，因此应适当使用这项服务 用于我们的“研究”项目。另一方面，我们已经开始与计算机科学家在不同的 中心利用人工智能（AI）/机器学习来量化淀粉样蛋白等病理发现 神经退行性疾病中的斑块和缠结。然而，由于无法使用全载玻片扫描仪， 阻碍了我们的进步与此同时，随着期望的产生，现在我们对 我们无法正确提供服务，并且在提交的P30预算中没有包括其成本。其次我们 我认识到有必要扩大我们的努力，收集死后脑脊液，以满足日益增长的需求， 这个有价值的标本，并协助我们的生物标志物核心为他们的生物标志物研究。 神经病理学核心活动继续快速增长，需要更全面的正式数据库 计划，以支持更高水平的核心文件和库存性能。最后，我们低估了 我们基本设备如组织处理器和切片机的退化率以及它们缺乏 在未来几年内，他们将获得制造商的技术支持。为了实现可持续发展，我们必须 用一台新的可靠的机器来取代它们，至少在未来10年内都能正常工作并得到支持。

PROJECT SUMMARY This Supplement requests one year of funding to support unforeseen costs associated with the University of Kansas Alzheimer’s Disease Research Center (KU ADRC) Neuropathology (NP) Core. The Neuropathology Core provides critical KU ADRC infrastructure in collaborating with other ADRC Cores (Figure 1). The neuropathology core function is essential to the Center’s mission and scientific theme by 1) Maintaining the autopsy program and Brain Bank; 2) Providing neuropathologic diagnosis, consultation, and training for investigators and trainees; 3) Obtaining dural and skin biopsies for induced pluripotent stem cell (IPSC) lines; and 4) Providing brain tissue for mitochondrial DNA (mtDNA) sequencing by the Biomarker Core. The NP Core continually upgrades it status to the diagnostic advances in the field and evolves according to the approved and accepted new guidelines, knowledge and state-of-the-art technology. Furthermore, the Core also participates in the important debates that produce these advances. An unanticipated growth in the number of investigators requesting NP Core support, an emergent unforeseen condition limiting our core to create a digital library of glass slides, increasing request for postmortem CSF specimens and an unpredicted obsolescence of our essential equipment to be replaced, predicates this request. We proposed in our recently funded P30 to provide open libraries of whole-slide scanned images to computer scientists and other investigators utilizing the scanners located in the department of pathology. However, due to increasing demand for neoplastic and other pathology specimens in the department, we have not been able to use this service properly as the current scanner is slow and the department cannot allocate proper time needed for our “research” projects. On the other hand, we have started working with computer scientists in different centers to utilize artificial intelligence (AI)/machine learning to quantify pathologic findings such as amyloid plaques and tangles in neurodegenerative diseases. However, the lack of access to a whole-slide scanner has incumbered our progress. Meanwhile, as the expectation was created, now we have increasing demand for a service we are unable to properly deliver and did not include its cost in submitted P30 budget. Secondly, we realize a need to extend our effort to collect postmortem cerebrospinal fluid to address increasing demand for this valuable specimen and assist our biomarker core for their biomarker studies. Neuropathology Core activities continue to rapidly grow, requiring a more comprehensive formal database program to support a higher level of Core documentation and inventory performance. Finally, we underestimated the rate of degeneration in our essential equipment such as tissue processor and microtome and their lack of extended technical support from their manufacturers for the coming years. For sustainable growth, we must replace them with a new reliable machine to be functional and supported for at least the next 10 years.