Fluid Biomarker Core

核心C：流体生物标志物项目摘要/摘要 生物标志物数据对于将阿尔茨海默病（AD）定义为一个连续体至关重要， 在认知症状发作之前数十年发展，最终发展为痴呆症。这 这一概念影响了疾病命名、诊断标准、预后潜力和临床试验 设计已提出修订诊断标准以纳入生物标志物结果， 增加AD作为临床损害的潜在病因的置信度，并允许诊断 AD在整个疾病连续体中，甚至可能在无症状期。本临床前研究中的个体 阶段（如ACS）作为预防试验的目标人群受到高度关注， 确定最有可能保留正常认知功能的疾病修饰疗法。 自研究开始以来，流体生物标志物核心（核心C）已经制定并实施了标准 标准化收集、储存、跟踪和分享信息的操作程序和高效工作流程 空腹CSF和血浆样本。ACS已经确定了生物标志物异常， 临床前AD，定义为这些变化在成人寿命期间何时发生以及它们如何进展。我们 我们现在准备扩大我们的分析，以表征临床前AD在其20多年的发展 当然，研究在临床前阶段观察到的生物标志物变化是否可以预测 转变为症状性AD，并评估可能加速或延迟这种转变的因素。未来 我们会继续提供基础设施， 用于收集、储存和分发样本至项目2（用于测量和评估 已建立的、新出现的和新的生物标志物[例如，炎症]以预测临床进展），以及 研究临床前AD的外部AD研究者。项目2中生成的流体生物标志物数据也将 其他ACS项目在研究生物标志物与成像测量的相关性时使用， 神经炎症（通过DBSI）和缠结负荷（通过tau PET）（项目1），肠道微生物组（项目3）和 身体活动和心血管风险因素（项目4）。与我们对生物标志物的强调一致， 为了保证检测的精确性、重现性和标准化，Core C还将进行年度检测验证， 支持项目2中进行的样品分析的批次桥接实验。我们还将继续 与其他国内和国际研究团体（工业，学术）的互动和合作 和临床），以促进样本采集方案协调所需的质量控制（QC）工作， 生物标志物测定标准化。为此，我们提出以下三个具体目标：1）继续 维持和培养禁食CSF和血浆的生物储存库，用于当前和未来的衰老和AD研究; 2)协调将CSF和血浆样本分发给合格的研究者;以及3）参与 关于流体生物标志物测定开发/验证以及方案QC和标准化工作的研究。

Core C: Fluid Biomarker Project Summary/Abstract Biomarker data have been critical for defining Alzheimer disease (AD) as a continuum, with pathology developing decades prior to the onset of cognitive symptoms that eventually progress to dementia. This concept has impacted disease nomenclature, diagnostic criteria, prognostic potential, and clinical trial design. Revisions in diagnostic criteria to incorporate biomarker results have been proposed in order to increase the confidence of AD as the underlying etiology of a clinical impairment and to permit a diagnosis of AD across the disease continuum, perhaps even in the asymptomatic period. Individuals in this preclinical stage (as in the ACS) are receiving intense focus as a targeted population for prevention trials aimed at identifying disease-modifying therapies that have the best chance of preserving normal cognitive function. Since study inception, the Fluid Biomarker Core (Core C) has developed and implemented standard operating procedures and efficient workflows for the standardized collection, storage, tracking and sharing of fasted CSF and plasma samples. The ACS has identified biomarker abnormalities that characterize preclinical AD, defined when these changes develop during the adult lifespan and how they progress. We are now poised to expand our analyses to characterize the progression of preclinical AD over its 20+ year course, investigate whether the biomarker changes observed during this preclinical period are predictive of transition to symptomatic AD, and assess factors that may accelerate or retard this transition. In the next funding cycle we will extend our proven track record for excellence by continuing to provide the infrastructure for the collection, storage, and distribution of samples to Project 2 (for the measurement and evaluation of established, emerging and novel biomarkers [e.g., inflammation] to predict clinical progression) and to outside AD investigators studying preclinical AD. Fluid biomarker data generated in Project 2 will also be used by other ACS Projects in their investigations of biomarker associations with imaging measures of neuroinflammation (via DBSI) and tangle load (via tau PET) (Project 1), the gut microbiome (Project 3) and physical activity and cardiovascular risk factors (Project 4). In keeping with our emphasis on biomarker assay rigor, reproducibility and standardization efforts, Core C will also perform annual assay validation and lot bridging experiments in support of sample analyses carried out in Project 2. We will also continue our interactions and collaborations with other domestic and international research groups (industrial, academic and clinical) to foster quality control (QC) efforts required for sample collection protocol harmonization and biomarker assay standardization. To this end, we propose the following three Specific Aims: 1) Continue to maintain and grow a biorepository of fasted CSF and plasma for present and future studies of aging and AD; 2) Coordinate the distribution of CSF and plasma samples to qualified investigators; and 3) Participate in studies regarding fluid biomarker assay development/validation and protocol QC and standardization efforts.