Repository Core

存储库核心

• 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
• 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' 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

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 不同类型脑白质偶发病变MRI的临床意义 有认知主诉的人群(确实)是为了识别进行性疾病的解剖学和生物调节器 脑白质(WM)损伤，使用精确医学方法在大型和 临床人群多样化。为了实现这一目标，将获得三个基本的生物学数据集：1) 协调神经成像数据以记录WM损伤的程度、位置和数量；2)液体生物标记物 评估包括炎症、内皮功能障碍和合并症在内的风险修饰物的数据 神经退行性疾病；以及3)使用多基因来测量固有遗传易感性的遗传数据 阿尔茨海默病(AD)和WM高信号(WMH)的风险分数以及已知的序列变体(例如 ApoE4和NOTCH3)。因此，存储库核心(RC)的目标是使用协调一致的方法来 收集、处理、存储、跟踪、分析和共享神经成像、生物标本和相关的遗传数据。 需要集中的核心服务，以有效支持研究任务并使科学 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 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 来自多个站点的5年以上将需要标准化的质量控制(QC)检查、数据跟踪和 与参与诊所现场的研究人员进行协调。委员会及其领导层和调查人员 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、专业和物理基础设施，通过执行以下四个步骤有效执行核心任务 明确的目标。在目标1中，资源中心将与NINDS、行政核心(AC)和合作诊所合作 现场制定和实施标准化的血液采集、加工、分项操作程序 通过利用现有的AD中心实现等分、冷冻、运输、长期存储和分发 计划、MarkVCID联盟和发现网络协议。在目标2中，我们将生成、存储 分析和分发与WM损伤和并存相关的血液生物标记物和遗传数据 神经退行性病变。在目标3中，我们将监督以下各项的获取、分析、质量控制和分发 协调的神经成像数据，将直接告知WM的进展速度和解剖特征 他们在认知障碍中的作用受到伤害。在目标4中，我们将与咨询委员会和统计核心合作，以出口 数据和样本信息，从而有助于与研究机构广泛分享数据和样本 社区。RC将确保数据和样本的一致完整性，以提供高水平的科学 结果的严谨性和可重复性。沉积的数据和生物标本将创造丰富和高质量的 未来分析的资源，新的生物标记物的发现，以及治疗意义的确定 WM损伤导致认知功能减退和痴呆的途径。