Repository Core

存储库核心

• 批准号: 10266152
• 负责人: LEE-WAY JIN
• 金额: $ 259.71万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 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/10266152
• 关键词: 3-Dimensional; Affect; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer’s disease biomarker; Amyloid beta-42; Anatomy; Bar Codes; Biological; Biological Markers; Blood; Blood specimen; Brain Injuries; Clinic; Clinical; Clinical Data; Cognitive; Collection; Communities; Cross-Sectional Studies; DNA; Data; Data Set; Databases; Dementia; Deposition; Derivation procedure; Ensure; Equipment and supply inventories; Freezing; Future; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genotype; Glial Fibrillary Acidic Protein; Goals; Impaired cognition; Individual; Inflammation; Inflammatory; Infrastructure; Interleukin-18; Leadership; Lesion; Light; Liquid substance; Location; Longitudinal Studies; Machine Learning; Magnetic Resonance Imaging; Measures; Mission; Modeling; NOTCH3 gene; National Institute of Neurological Disorders and Stroke; Nerve Degeneration; Pathology; Pathway interactions; Phenotype; Plasma; Population; Population Heterogeneity; Procedures; Process; Protocols documentation; Quality Control; 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; base; 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; standardize measure; synergism; tau Proteins; vascular risk factor; white matter; white matter injury

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 上偶发白质病变的临床意义的总体目标 患有认知疾病的人群（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 多样化的临床人群。为了实现这一目标，将获得三个重要的生物数据集：1) 协调神经影像数据以记录 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 APOE4 和 NOTCH3)。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有效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。收集数据/样本 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 与参与诊所的研究人员进行协调。 RC 及其领导层和调查员 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，通过执行四个任务来有效地履行核心使命 具体目标。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 神经退行性疾病。在目标 3 中，我们将监督数据的采集、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 损害他们在认知障碍中的作用。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 社区。 RC 将确保数据和样本的一致完整性，从而提供高水平的科学依据 结果的严谨性和可重复性。存入的数据和生物样本将创造出丰富且高质量的数据。 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。