Repository Core

项目摘要-存储库核心 在不同的MRI检查中，INCIDENTAL白色病变的临床意义的总体目标是 有认知主诉的人群（INDEED）是为了确定进行性认知功能障碍的解剖学和生物学调节剂。 白色物质（WM）损伤，驱动认知障碍，使用精确医学方法在一个大的， 不同的临床人群。为了实现这一目标，将获得三个基本的生物数据集：1） 协调神经影像学数据，以记录WM损伤的程度、位置和数量; 2）液体生物标志物 评估风险修饰因子的数据，包括炎症、内皮功能障碍和共病 神经退行性病症;和3）使用多基因测序技术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）的风险评分以及已知的序列变体（例如， APOE 4和NOTCH 3）。因此，知识库核心（RC）的目标是使用统一的方法， 收集、处理、存储、跟踪、分析和共享神经成像、生物标本和相关遗传数据。 需要集中的核心服务来有效地支持研究使命，并使科学 这种规模的项目需要协同作用，其中将从2，250个不同的样本和数据中获得 在三个时间点对全国范围内的受试者进行了调查，总共有6，750个数据/样本集。收集数据/样本 来自多个研究中心超过5年的数据将需要标准化的质量控制（QC）检查、数据跟踪， 与参与临床试验机构的研究人员协调。驻地协调员及其领导和调查人员 在管理NINDS MarkVCID联盟和ADRC核心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，通过执行四项任务，有效地执行核心使命 明确的目标。在目标1中，RC将与NINDS、行政核心（AC）和合作诊所合作 研究中心制定并实施血液采集、处理、分装、 通过利用现有的AD中心进行分装、冷冻、运输、长期存储和配送 程序、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 神经退行性病变在目标3中，我们将监督采购、分析、质量控制和分发 协调的神经影像学数据，将直接告知WM的进展速度和解剖特征 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， 数据和样本信息，从而有助于与研究广泛共享数据和标本 社区RC将确保数据和样本的一致完整性， 严格性和结果的可重复性。所保存的数据和生物标本将为我们提供丰富和高质量的 用于未来分析、新生物标志物发现和治疗意义鉴定的资源 这些通路是WM损伤导致认知能力下降和痴呆的基础。

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.