Biomarker Core

生物标志物核心

• 批准号: 10461126
• 负责人: LEE-WAY JIN
• 金额: $ 32.27万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10461126
• 关键词: Alzheimer' s Disease; Alzheimer' s disease pathology; Amyloid; Amyloid beta-Protein; Bar Codes; Biological; Biological Markers; Blood; Blood specimen; Brain Injuries; Clinical; Clinical Trials; Cognitive; Cognitive aging; Collaborations; Collection; Communities; Complex; Computer software; DNA; Data; Databases; Dementia; Deposition; Diagnostic; Disease; Elderly; Epidemiology; Equipment and supply inventories; Faculty; Freezing; Funding; Genetic; Goals; Grant; Heterogeneity; Impaired cognition; Individual; Infrastructure; Intervention; Life; Longitudinal cohort; Mentors; Outcome; Pathologic Processes; Pathology; Phenotype; Plasma; Population Heterogeneity; Procedures; Process; RNA; Regulation; Research; Research Personnel; Resource Sharing; Resources; Retrieval; Sampling; Secure; Serum; Specimen; Standardization; Study Subject; System; Technology; Time; Validation; Work; accurate diagnosis; base; biobank; biomarker discovery; blood-based biomarker; career development; cohort; cost efficient; data sharing; epidemiology study; frontier; glycoproteomics; indexing; innovation; lipidomics; metabolomics; multi-ethnic; multiple omics; neuroimaging; novel marker; operation; programs; protein biomarkers; racial and ethnic; repository; research and development; response biomarker; risk prediction model; saliva sample; sample collection; specific biomarkers; standardize measure; tau Proteins; tau-1; tool; web based interface; web portal

PROJECT SUMMARY – Biomarker Core The overarching goal of the UCD ADRC is to understand the multiple and complex determinants that explain heterogeneity of cognitive trajectories and progression to dementia among a cohort of diverse older adults. In line with this goal, our study subjects form a diverse multi-ethnic/racial longitudinal cohort. To be able to offer disease-modifying interventions in the subject’s lifetime, a precise and dynamic biological definition of the subject’s disease trajectory is essential. It requires a comprehensive biomarker assessment of both AD pathology and non-AD specific brain injury that may contribute to and modify the trajectories of cognitive decline. This task is particularly critical when faced with mixed pathological processes manifested by subjects of diverse backgrounds. To meet this challenge, the UC Davis ADRC launched a biorepository in 2014 to collect blood specimens and establish standard operation procedures. We have since grown substantially in expertise and sample collection via continuous funding through several NIA- and Alzheimer’s Association- funded blood biomarker, clinical trial, and epidemiological projects, as well as participation in national programs such as MarkVCID, ADNI, NCRAD, and AD Metabolomic Consortium. Currently we have deposited thousands of blood specimens (serum, plasma, DNA, and RNA) from 1279 subjects in our ADRC Longitudinal Cohort; hundreds of them have given longitudinal samples. We have also collected saliva and blood samples from hundreds of subjects participating in ADRC-affiliated clinical trials and epidemiological projects such as the Life After 90 Study. Sample categorization, inventory, tracking, and retrieval are conducted by the barcode-based OpenSpecimen network software, which is further integrated into the ADRC Web-based interface. Moreover, we have established expertise in ultra-sensitive protein biomarker analysis using SiMoA technology, and built a broad multi-omics platform for collaboration by providing expertise and resources for emerging omics technology including glycomics, glycoproteomics, lipidomics, and metabolomics. In this ADRC application, we will formally establish the Biomarker Core (BC), which will accomplish the following four specific aims: Aim 1 – to expand the repository of high-quality samples from diverse populations; Aim 2 – to quantify and integrate essential and emerging blood biomarkers to support diagnostics and theragnostics efforts of ADRC; Aim 3 – to provide infrastructure to support novel biomarker discovery, clinical trials, and UCD ADRC-affiliated clinical and epidemiological projects; and Aim 4 – to extend our existing robust and cost-efficient systems for sharing data and specimens broadly with the research community to support innovative research and career development. We believe the deposited data and specimens from our diverse multi-ethnic/racial longitudinal cohort will constitute a unique, readily sharable resource to enable cognitive stage-dependent analyses of inter-related biomarkers in data- and hypothesis-driven studies. Our expertise in SiMoA, glycomics, lipidomics, and metabolomics will help investigators nationwide to advance into new frontiers of biomarker discovery.

项目摘要 – 生物标记核心 UCD ADRC 的首要目标是了解解释多个复杂的决定因素 一组不同老年人的认知轨迹异质性和痴呆进展。在 为了实现这一目标，我们的研究对象形成了一个多元化的多民族/种族纵向队列。能够提供 在受试者一生中进行疾病缓解干预措施，这是对疾病的精确和动态的生物学定义 受试者的疾病轨迹至关重要。它需要对 AD 和 AD 进行全面的生物标志物评估 病理学和非 AD 特异性脑损伤可能有助于和改变认知轨迹 衰退。当面对受试者表现出的混合病理过程时，这项任务尤其重要 的不同背景。为了应对这一挑战，加州大学戴维斯分校 ADRC 于 2014 年推出了一个生物样本库 采集血液样本并建立标准操作程序。此后，我们在以下领域取得了长足发展： 通过多个 NIA 和阿尔茨海默病协会的持续资助，获得专业知识和样本收集 资助血液生物标志物、临床试验和流行病学项目，以及参与国家计划 例如 MarkVCID、ADNI、NCRAD 和 AD 代谢组学联盟。目前我们已存入数千 来自 ADRC 纵向队列中 1279 名受试者的血液样本（血清、血浆、DNA 和 RNA）； 其中数百人提供了纵向样本。我们还采集了患者的唾液和血液样本 数百名受试者参加 ADRC 附属临床试验和流行病学项目，例如 Life 90后学习。样品分类、库存、跟踪和检索是通过基于条形码的 OpenSpecimen 网络软件，进一步集成到 ADRC 基于 Web 的界面中。而且， 我们已经建立了使用 SiMoA 技术进行超灵敏蛋白质生物标志物分析的专业知识，并建立了 通过为新兴组学提供专业知识和资源，建立广泛的多组学协作平台 技术包括糖组学、糖蛋白质组学、脂质组学和代谢组学。在此 ADRC 应用程序中，我们 将正式建立生物标志物核心（BC），它将实现以下四个具体目标： 目标 1 – 扩大来自不同人群的高质量样本库；目标 2 – 量化和整合 支持 ADRC 诊断和治疗诊断工作的重要和新兴血液生物标志物；目标 3 – 达到 提供基础设施来支持新的生物标志物发现、临床试验以及都柏林大学 ADRC 附属的临床和 流行病学项目；目标 4 – 扩展我们现有的强大且经济高效的数据共享系统 以及与研究界广泛合作的标本，以支持创新研究和职业发展。 我们相信，来自我们不同的多民族/种族纵向队列的存储数据和样本将 构成了一种独特的、易于共享的资源，可以对相互关联的认知阶段进行分析 数据和假设驱动研究中的生物标志物。我们在 SiMoA、糖组学、脂质组学和 代谢组学将帮助全国的研究人员进入生物标志物发现的新领域。