Biomarker Core

生物标记核心将通过管理生物样本在拟议的耶鲁 ADRC 中发挥关键作用 由标准和新型生物样本组成的存储库，并通过开发和应用 尖端的蛋白质组学和表观遗传学分析以及生物信息学方法来整合高维 多组学数据。耶鲁 ADRC 生物标记核心管辖下的方法和生物样本将 促进阿尔茨海默病（AD）易感性的有前途的生物标志物的开发和验证， 改善 AD 风险预测，并确定有针对性的干预措施发展的有希望的方向。的 Biomarker Core将与数据管理和统计核心（DMSC）在管理方面密切合作 生物样本库。我们还将促进多组学数据与生成的数据的整合 由临床和成像核心评估和验证标准和新型生物标志物 捕捉 AD 异质性、易感性和进展。我们将与 DMSC 合作，利用统计数据 认知轨迹和衰退的建模，和/或死亡选择或其他偏差的考虑 评估 AD 相关生物标志物的可靠性、有效性和普遍性。最后，我们将与 教育部分和外展核心，以促进 AD 生物标志物采集和外展方面的培训和外展 使用。具体目标包括： 目标 1：管理耶鲁 ADRC 生物样本库。与 临床、神经病理学、DMS 核心和 NCRAD，我们将管理耶鲁 ADRC 生物样本库和 向 ADRC 和非 ADRC 研究人员提供生物样本。目标 2：评估、跟踪和验证生物流体和 AD 的组织生物标志物。我们将使用基于 ELISA 的标准化检测方法来检测 Abeta1-40、Abeta1-42、t-tau 和 p- tau 存在于耶鲁大学 ADRC 生物样本库现有和未来的生物流体样本中的 CSF 中，并利用最先进的 艺术靶向质谱分析用于分析生物体液和脑组织中选定的生物标志物 耶鲁 ADRC 生物储存库和其他 ADRC 附属研究项目。目标 3：评估、跟踪和验证 基于高维组学数据的系统级生物标志物。我们将评估 DNA 甲基化 (DNAm) 来自耶鲁 ADRC 生物储存库和其他 ADRC 附属研究项目的生物流体，并用它来计算 表观遗传年龄和 AD 异质性的经过验证和新颖的生物标志物测量。与 DMSC，我们将使用系统生物学方法将 DNAm 和蛋白质组数据与可用数据整合 通过临床和成像核心。目标 4：促进 AD 生物标志物采集和推广方面的培训和推广 使用。

The Biomarker Core will play a key role in the proposed Yale ADRC by managing the Biospecimen Repository consisting of both standard and novel biospecimens, and through the development and application of cutting-edge proteomic and epigenetic assays and bioinformatics approaches to integrate high-dimensional multi-omics data. Methods and biospecimens under the jurisdiction of the Yale ADRC Biomarker Core will facilitate the development and validation of promising biomarkers of Alzheimer’s disease (AD) susceptibility, improve AD risk prediction, and identify promising directions for development of targeted interventions. The Biomarker Core will work closely with the Data Management and Statistics Core (DMSC) in the management of the Biospecimens Repository. We will also facilitate the integration of multi-omics data with data generated by the Clinical and Imaging Cores to assess and validate both standard and novel biomarkers aimed at capturing AD heterogeneity, susceptibility, and progression. We will work with the DMSC to utilize statistical modeling of cognitive trajectories and decline, and/or considerations of mortality selection or other biases when evaluating the reliability, validity, and generalizability of AD-related biomarkers. Finally, we will work with the Education Component and Outreach Core to facilitate training and outreach in AD Biomarker acquisition and use. Specific Aims include: Aim 1: Manage Yale ADRC Biospecimen Repository. Working closely with the Clinical, Neuropathology, and DMS Cores, and NCRAD, we will manage the Yale ADRC biorepository and provide biospecimens to ADRC and non-ADRC investigators. Aim 2: Assess, track and validate biofluid and tissue biomarkers of AD. We will use standardized ELISA-based assays for Abeta1-40, Abeta1-42, t-tau and p- tau in CSF in existing and future biofluid samples from Yale ADRC Biorepository, as well as utilize state-of-the- art targeted mass spectrometric assays to analyze selected biomarkers in biofluid and brain tissue from the Yale ADRC Biorepository and other ADRC-affiliated research projects. Aim 3: Assess, track and validate systems-level biomarkers based on high-dimensional omics data. We will assess DNA methylation (DNAm) in biofluids from the Yale ADRC Biorepository and other ADRC-affiliated research projects, and use it to calculate both validated and novel biomarker measures of epigenetic age and AD heterogeneity. Working with the DMSC, we will use systems biology approaches to integrate the DNAm and proteomic data with data available via the Clinical and Imaging Cores. Aim 4: Facilitate training and Outreach in AD Biomarker acquisition and use.