Biological heterogeneity in ADRD

摘要 华盛顿大学ADRC的驱动科学重点是研究ADRD的生物异质性--其机制 疾病病理生理学的生物学基础以及对抗退化的因素 和痴呆症。我们的中心是最早认识到阿尔茨海默病病因异质性的中心之一2， 这一重点仍然迫切需要。新的技术和范式已经出现， ADRD的发病机制，并需要充分表征的人类受试者和精心策划的生物标本。 我们的核心研究资源的拟议组织框架是多学科ADRD 表型分析整合的四个关键学科是遗传学，认知，地形/解剖学， 神经病理学的在这个框架中，脑空间是AD的其他生物标志物的整合点，如 不同病理的程度和位置是最切实和客观的表现， 不同病理生理学途径的结果。因此，我们工作的一个关键方面将包括整合 生物标志物在大脑皮层上延伸，如从成像和神经病理学得到的， 生物标记、认知和遗传信息。一个重要的目标是支持更好的AD分层 表型，以推进候选AD机制的研究。 华盛顿大学ADRC是唯一准备承担这项工作，其中包括历史优势， 该中心和华盛顿大学的研究资源，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 正在提出通过技术、方法和技术创新， 和信息学。这些包括干细胞和精密神经病理学中的精密组学组件 核心，临床核心中的心理测量学组件，新成像和生物标记中的信息学专业知识 核心和研究教育部分的开放神经科学研讨会。 我们中心的理念是不仅通过失去的透镜， 什么是保留的，以及相关的保留优势。这种观点渗透到我们的中心，从激励 我们对恢复力和解剖学保留的生物学和机械学基础的兴趣， 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国印第安人和阿拉斯加原住民的ADRD。基础上 我们在过去5年的成功努力，我们计划扩大我们的宣传工作，以土著部落， 组织在华盛顿州，以提高他们的准备ADRD研究，并作出重点 努力理解和开发模型，以克服生物标本收集和数据共享的障碍 在这个人群中。

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.