Biological heterogeneity in ADRD

ADRD 的生物异质性

• 批准号: 9921703
• 负责人: Thomas J. Grabowski
• 金额: $ 300.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9921703
• 关键词: Abbreviations; Alaska Native; Alzheimer' s Disease; Alzheimer' s disease related dementia; American Indians; Anatomy; Automobile Driving; Autopsy; Biological; Biological Markers; Brain; Cellular biology; Cerebral cortex; Cerebrum; Clinical; Cognition; Cognitive; Collection; Communities; Data; Data Set; Dementia; Discipline; Disease; Educational workshop; Etiology; Fostering; Frontotemporal Dementia; Functional disorder; Genetic; Goals; Heterogeneity; Image; Informatics; Investigation; Letters; Liquid substance; Location; Medical; Medical center; Memory; Methods; Modeling; National Institute on Aging; Nerve Degeneration; Neurosciences; Outcome; Participant; Pathology; Pathway interactions; Phenotype; Philosophy; Population; Preventive treatment; Process; Psychometrics; Quality Control; Readiness; Research; Research Personnel; Resistance; Resources; Stratification; Techniques; Time; Training; Tribes; Universities; Washington; Wellness Center; Work; base; biological heterogeneity; cell repository; data management; data sharing; education research; effective therapy; genetic information; human subject; imaging biomarker; improved; innovation; interest; lens; medical schools; multidisciplinary; neuropathology; new technology; next generation; outreach; precision medicine; programs; recruit; research study; resilience; statistics; stem cells

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.

抽象的 UW ADRC的驾驶科学重点是研究ADRD的生物异质性 - 机械 疾病病理生理学的生物基础以及反变性的因素 和痴呆症。我们的中心是最早认识到阿尔茨海默氏病的病因异质性的人之一。2 仍然需要这种重点。新技术和范式已经出现以分析生物学 ADRD的机制，需要良好特征的人类受试者和精心策划的生物测量。 我们核心研究资源的拟议组织框架是多学科的ADRD 表型。综合的四个关键学科是遗传，认知，地形/解剖学和 神经病理学。在此框架中，大脑空间是AD其他生物标志物的整合点，如 不同病理的大小和位置是最有形，最客观的表现 不同病理生理途径的结果。我们工作的关键方面将包括整合 生物标志物延伸到大脑皮质上，源自成像和神经病理学，并具有液体 生物标志物，认知和遗传信息。一个重要的目标是支持更好的广告分层 促进候选AD机制研究的表型。 UW ADRC独特地进行了这项工作，其中结合了历史优势 UW的中心和研究资源，利用核心线索的集体专业知识和 主任，以及从新的技术能力中受益，使我们能够实施此计划。新组件 有人提议通过技术，方法， 和信息。这些包括精度神经病理学中的干细胞和精度 - 词素成分 核心，临床核心中的心理计量学组件，新成像和生物标志物的信息学专业知识 研究教育部分的核心和开放的神经科学研讨会。 我们中心的哲学是不仅要通过丢失的镜头来查看Adrd，还可以通过 幸免的东西以及相关的保留优势。这种观点渗透到我们的中心，激励 我们对弹性和解剖学的生物学和机械基础的兴趣，对外展工作 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。建立 在过去的5年中，我们成功的努力，我们计划将我们的外展工作扩展到本地部落和 华盛顿州的组织，提高其对ADRD研究的准备，并进行重点 努力理解和开发模型，以克服生物测量收集和数据共享的障碍 在这个人群中。