Repository Core

存储库核心

基本信息

批准号：
10489297
负责人：
LEE-WAY JIN
金额：
$ 391.23万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10489297
关键词：
3-Dimensional Affect Alzheimer&apos s Disease Alzheimer’s disease biomarker Amyloid beta-42 Anatomy Bar Codes Biological Biological Markers Blood Blood specimen Brain Injuries Categories Clinic Clinical Clinical Data Cognitive Collaborations Collection Communities DNA Data Data Set Databases Dementia Deposition Derivation procedure Ensure Equipment and supply inventories Freezing Future Genetic Genetic Predisposition to Disease Genotype Glial Fibrillary Acidic Protein Goals IL18 gene Impaired cognition Individual Inflammation Inflammatory Infrastructure Leadership Lesion Light Liquid substance Location Longitudinal Studies Machine Learning Magnetic Resonance Imaging Measures Mission NOTCH3 gene National Institute of Neurological Disorders and Stroke Nerve Degeneration Pathology Pathway interactions Phenotype Plasma Population Population Heterogeneity Procedures Process Protocols documentation Qualifying Quality Control Recommendation Regulation Reproducibility of Results Research Research Personnel Research Support Resource Sharing Resources Retrieval Risk Role Sampling Secure Services Shipping Site Specimen Standardization System Therapeutic Time Validation Variant White Matter Hyperintensity Work apolipoprotein E-4 biomarker discovery clinical research site clinically significant comorbidity cost efficient data integrity data sharing endothelial dysfunction exome sequencing experience genome-wide interest neurofilament neuroimaging novel marker polygenic risk score precision medicine programs recruit repository risk prediction model standardize measure synergism tau Proteins vascular risk factor white matter white matter injury

项目摘要

PROJECT SUMMARY – Repository Core The overarching goal of the Clinical significance of INciDEntal white matter lEsions on MRI in a Diverse population with cognitive complaints (INDEED) is to identify anatomic and biologic modulators of progressive white matter (WM) injury that drive cognitive impairment using a precision medicine approach in a large and diverse clinical population. To achieve this goal, three essential biological datasets will be acquired: 1) harmonized neuroimaging data to document the degree, location, and amount of WM injury; 2) fluid biomarker data to evaluate risk modifiers including inflammation, endothelial dysfunction, and co-morbid neurodegenerative conditions; and 3) genetic data to measure intrinsic genetic susceptibility using polygenic risk scores for Alzheimer's disease (AD) and WM hyperintensities (WMH) and known sequence variants (e.g. APOE4 and NOTCH3). The goal of the Repository Core (RC), therefore, is to use harmonized approaches to collect, process, store, track, analyze, and share neuroimaging, biospecimens and associated genetic data. Centralized core services are needed to effectively support the research mission and enable the scientific synergy necessary for a project of this scale, in which samples and data will be obtained from 2,250 diverse subjects nationwide at three time points, for a total of up to 6,750 data/sample sets. Collecting data/samples from multiple sites over 5 years will require standardized quality control (QC) checks, data tracking, and coordination with research staff at participating clinic sites. The RC, with its leadership and investigators experienced in managing similar tasks in the NINDS MarkVCID Consortium and ADRC Cores, will provide the technical, professional, and physical infrastructure to effectively implement the core mission by executing four specific aims. In Aim 1, the RC will work with NINDS, the Administrative Core (AC), and the collaborating clinic sites to develop and implement standardized operating procedures for blood collection, processing, sub- aliquoting, freezing, shipping, long-term storage, and distribution, by leveraging the existing AD Centers Program, MarkVCID Consortium, and DISCOVERY Network protocols. In Aim 2, we will generate, store, analyze, and distribute blood biomarker and genetic data relevant to WM injury and co-morbid neurodegenerative pathologies. In Aim 3, we will oversee acquisition, analysis, QC, and distribution of harmonized neuroimaging data that will directly inform the rate of progression and anatomic features of WM injury to their role in cognitive impairment. In Aim 4, we will work with the AC and the Statistical Core to export data and sample information, thus contributing to the sharing of data and specimens broadly with the research community. The RC will ensure consistent integrity of data and samples that will deliver a high level of scientific rigor and the reproducibility of results. The deposited data and biospecimens will create a rich and high-quality resource for future analyses, novel biomarker discovery, and identification of therapeutically significant pathways that underlie the contribution of WM injury to cognitive decline and dementia.

项目摘要 – 存储库核心 MRI 上偶然的白质病变在不同疾病中的临床意义的总体目标认知障碍人群（INDEED）的目的是识别进行性认知障碍的解剖学和生物调节因子使用精准医学方法在大范围内导致认知障碍的白质（WM）损伤为了实现这一目标，将获得三个基本的生物数据集：1) 统一的神经影像数据记录 WM 损伤的程度、位置和数量；2) 液体生物标志物；评估风险调节因素的数据，包括炎症、内皮功能障碍和共病神经退行性疾病；3) 使用多基因测量内在遗传易感性的遗传数据阿尔茨海默病 (AD) 和 WM 高信号 (WMH) 以及已知序列变异（例如因此，存储库核心 (RC) 的目标是使用统一的方法来收集、处理、存储、跟踪、分析和共享神经影像、生物样本和相关遗传数据。需要集中的核心服务来支持研究任务并实现科学发展这种规模的项目需要协同作用，其中样本和数据将从 2,250 个不同的国家获得全国范围内三个时间点的受试者，总共多达 6,750 个数据/样本集。超过 5 年来自多个地点的数据将需要标准化的质量控制 (QC) 检查、数据跟踪和与参与临床中心的研究人员及其领导层和研究人员进行协调。在管理 NINDS MarkVCID 联盟和 ADRC 核心中的类似任务方面经验丰富，将提供技术、专业和物质基础设施，通过执行四个方面有效地履行核心使命在目标 1 中，RC 将与 NINDS、行政核心 (AC) 和合作诊所合作。制定和实施血液采集、处理、分装的标准化操作程序的场所利用现有的 AD 中心进行分装、冷冻、运输、长期储存和分销计划、MarkVCID 联盟和 DISCOVERY 网络协议在目标 2 中，我们将生成、存储、分析和分发与 WM 损伤和共病相关的血液生物标志物和遗传数据在目标 3 中，我们将监督神经退行性病理学的获取、分析、质量控制和分发。统一的神经影像数据将直接告知 WM 的进展速度和解剖特征在目标 4 中，我们将与 AC 和统计核心合作导出。数据和样本信息，从而有助于研究中广泛共享数据和样本 RC 将确保数据和样本的一致性，从而提供高水平的科学成果。结果的严谨性和可重复性将产生丰富且高质量的数据和生物样本。未来分析、新生物标志物发现和治疗意义鉴定的资源 WM 损伤导致认知能力下降和痴呆的潜在途径。