Biological heterogeneity in ADRD

ADRD 的生物异质性

• 批准号: 10433865
• 负责人: Thomas J. Grabowski
• 金额: $ 293.35万
• 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/10433865
• 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 华盛顿大学 ADRC 的科学重点是研究 ADRD 的生物异质性 - 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 仍然迫切需要这一重点。分析生物的新技术和范式已经出现 ADRD 的机制，需要明确特征的人类受试者和精心策划的生物样本。 我们的核心研究资源拟议的组织框架是多学科 ADRD 表型分析。需要整合的四个关键学科是遗传学、认知学、地形/解剖学和 神经病理学。在这个框架中，大脑空间是 AD 其他生物标志物的整合点，如 不同病变的严重程度和部位是疾病最具体、最客观的表现。 不同病理生理途径的结果。因此，我们工作的一个关键方面将包括整合 来自成像和神经病理学的生物标志物延伸到大脑皮层，其中有液体 生物标志物、认知和遗传信息。一个重要目标是支持 AD 更好的分层 表型以推进候选 AD 机制的研究。 华盛顿大学 ADRC 已准备好承担这项工作，该工作融合了以下领域的历史优势： 华盛顿大学的中心和研究资源，利用核心领导者和 总监，并受益于使我们能够实施该计划的新技术能力。新组件 正在提议通过技术、方法的创新来带来致力于桥接学科的专业知识， 和信息学。其中包括精准神经病理学中的干细胞和精准组学成分 临床核心中的核心、心理测量学组成部分、新成像和生物标记中的信息学专业知识 研究教育部分的核心和开放神经科学研讨会。 我们中心的理念是不仅通过失去的东西来看待ADRD，而且通过 哪些是幸免的，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护的生物学和机械基础的兴趣，以及外展工作 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洲印第安人和阿拉斯加原住民的 ADRD。建立在 鉴于我们过去 5 年的成功努力，我们计划将我们的外展工作扩展到原住民部落和 华盛顿州的组织，以提高他们对 ADRD 研究的准备程度，并制定有针对性的 努力理解和开发模型以克服生物样本收集和数据共享的障碍 在这个人群中。