Biomarker Core

项目摘要-生物标志物核心 UCD ADRC的总体目标是了解解释这些问题的多重和复杂的决定因素。 认知轨迹的异质性和不同老年人队列中痴呆的进展。在 根据这一目标，我们的研究对象形成了一个多样化的多民族/种族纵向队列。能够提供 在受试者的一生中进行疾病修饰干预，这是一个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患者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的轨迹， 下降当面对受试者表现出的混合病理过程时， 不同的背景。为了应对这一挑战，加州大学戴维斯分校ADRC于2014年推出了生物储存库， 采集血液标本，建立标准操作规程。从那以后，我们在 通过几个NIA和阿尔茨海默氏症协会的持续资助， 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 如MarkVCID、ADNI、NCRAD和AD代谢组学联合体。目前，我们已向数千名 来自我们的ADRC纵向队列中的1279名受试者的血液标本（血清、血浆、DNA和RNA）; 其中数百人提供了纵向样本。我们还收集了来自 数百名受试者参加了ADRC附属的临床试验和流行病学项目，如生命 90后学习样本分类、库存、跟踪和检索由基于条形码的 OpenSpecimen网络软件，进一步集成到ADRC基于Web的界面中。此外，委员会认为， 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，建立广泛的多组学合作平台 包括糖组学、糖蛋白质组学、脂质组学和代谢组学的技术。在这个ADRC应用中，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的诊断和治疗不确定性工作的基本和新兴血液生物标志物;目标3- 提供基础设施，以支持新的生物标志物发现，临床试验，和UCD ADRC附属临床和 目标4-扩展现有稳健而具成本效益的数据分享系统 和标本广泛与研究界，以支持创新的研究和职业发展。 我们相信，来自我们多样化的多民族/种族纵向队列的储存数据和标本将 构成一个独特的，易于共享的资源，使认知阶段相关的分析， 生物标志物在数据和假设驱动的研究。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。

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.