Biological heterogeneity in ADRD

摘要 UW ADRC的主要科学重点是调查ADRD的生物异质性--机械 以及疾病病理生理学的生物学基础以及抗退行性变的因素 和痴呆症。我们的中心是最早认识到阿尔茨海默病的病因异质性的中心之一。 这种关注仍然是迫切需要的。已经出现了分析生物学的新技术和新范式 ADRD的机制，并需要具有良好特征的人类受试者和精心策划的生物标本。 我们核心研究资源的拟议组织框架是多学科ADRD 表型鉴定。需要整合的四个关键学科是遗传学、认知学、地形学/解剖学和 神经病理学。在这个框架中，大脑空间是AD的其他生物标志物的集成点，如 不同病理的大小和位置是最有形和客观的表现 不同病理生理途径的转归。因此，我们工作的一个关键方面将包括 生物标志物延伸到大脑皮层，如从影像和神经病理学中得出的，带有液体 生物标志物、认知和遗传信息。一个重要目标是支持更好地对AD进行分层 促进AD候选机制研究的表型。 UW ADRC独一无二地准备承担这项工作，这项工作结合了 华盛顿大学的中心和研究资源，利用核心领导和 董事，并受益于新的技术能力，使我们能够实施这一计划。新组件 正被提议通过技术、方法、技术的创新带来致力于连接学科的专业知识， 和信息学。其中包括干细胞和精密神经病理学中的精密组学成分。 核心，临床核心中的心理测量学组件，新成像和生物标志物中的信息学专业知识 研究教育部分的核心和开放式神经科学研讨会。 我们中心的理念是不仅通过失去的镜头来看待ADRD，而且通过 所保留的内容以及相关保留的优势。这一观点渗透到我们的中心，从激励 我们对复原力和解剖保留的生物学和机械基础的兴趣，到外展努力 ADRC及其相关的记忆和大脑健康中心。 我们中心的另一个重要主题是美洲印第安人和阿拉斯加原住民的ADRD。在基础上建设 我们在过去5年中的成功努力，我们计划将我们的外展努力扩展到土著部落和 华盛顿州的组织，以改善其对ADRD研究的准备，并使重点 努力了解和开发模型，以克服生物多样性收集和数据共享方面的障碍 在这群人中。

Abstract The UW ADRC's driving scientific focus is investigating the biological heterogeneity of ADRD – the mechanistic and biological underpinnings of the pathophysiology of disease as well as the factors countering degeneration and dementia. Our Center was one of the first to recognize etiologic heterogeneity in Alzheimer's disease2 and this focus is still urgently needed. New technologies and paradigms have emerged to analyze biological mechanisms of ADRD, and require well characterized human subjects and well-curated biospecimens. The proposed organizing framework for our core research resources is multi-disciplinary ADRD phenotyping. The four key disciplines to integrate are genetic, cognitive, topographic/anatomic, and neuropathologic. In this framework, the brain space is the point of integration of the other biomarkers of AD, as the magnitude and location of the different pathologies are the most tangible and objective manifestation of the outcome of different pathophysiological pathways. Thus a key aspect of our work will include integrating biomarkers extended over the cerebral cortex, as derived from imaging and neuropathology, with fluid biomarkers, cognitive and genetic information. An important goal is to support better stratification of AD phenotypes to advance investigation of candidate AD mechanisms. The UW ADRC is uniquely poised to undertake this work, which incorporates the historical strengths of the Center and research resources of the UW, leverages the collective expertise of the Core Leads and the Director, and benefits from new technical abilities that enable us to implement this program. New components are being proposed to bring expertise dedicated to bridging disciplines by innovations in techniques, methods, and informatics. These include Stem Cell and Precision -omics components in the Precision Neuropathology Core, Psychometrics component in the Clinical Core, Informatics expertise in the new Imaging and Biomarker Core and an Open Neuroscience workshop in the Research Education Component. Our Center's philosophy is to view ADRD not only through the lens of what is lost, but also through what is spared, and the associated retained strengths. This perspective permeates our Center, from motivating our interest in the biological and mechanistic basis of resilience and anatomic sparing, to the outreach efforts of the ADRC and its associated Memory and Brain Wellness Center. Another important theme of our Center is ADRD in American Indians and Alaska Natives. Building on our successful efforts in the last 5 years, we plan to extend our outreach efforts to Native tribes and organizations in Washington State, to improve their readiness for ADRD research, and to make a focused effort to understand and develop models to overcome the barriers to biospecimen collection and data sharing in this population.