Biomarker Core

Biomarker Core将通过管理Biosecimen在拟议的耶鲁ADRC中发挥关键作用 由标准和新型生物标本组成的资源库，并通过开发和应用 尖端蛋白质组和表观遗传学分析以及生物信息学方法，以整合高维 多组学数据。耶鲁ADRC生物标记物核心遗嘱管辖下的方法和生物检疫 促进开发和验证阿尔茨海默病(AD)易感性的有前景的生物标记物， 改进AD风险预测，并确定有希望的方向，以发展有针对性的干预措施。这个 BioMarker Core将在管理方面与数据管理和统计核心(DMSc)密切合作 生物制品储存库。我们还将促进多组学数据与生成的数据的集成 由临床和影像中心评估和验证标准和新型生物标记物 捕捉AD的异质性、易感性和进展。我们将与DMSC合作，利用统计 认知轨迹和下降的建模，和/或考虑死亡率选择或其他偏差时 评价AD相关生物标志物的信度、效度和概括性。最后，我们将与 教育部分和外联核心，以促进AD生物标记物获取和推广方面的培训和推广 使用。具体目标包括：目标1：管理耶鲁ADRC生物库。与美国政府密切合作 临床、神经病理学和DMS核心，以及NCRAD，我们将管理耶鲁ADRC生物信息库和 向ADRC和非ADRC调查人员提供生物检疫制剂。目标2：评估、跟踪和验证生物流体和 AD的组织生物标志物。我们将对Abeta1-40、Abeta1-42、t-tau和p-tau进行标准化的酶联免疫吸附测定。 来自耶鲁ADRC生物仓库的现有和未来生物流体样本中的脑脊液中的tau，以及利用最新的 ART靶向质谱分析生物体液和脑组织中选定的生物标记物 耶鲁ADRC生物库和其他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)在 来自耶鲁ADRC生物库和其他ADRC附属研究项目的生物流体，并使用它来计算 表观遗传年龄和AD异质性的验证和新的生物标记物测量。使用 ，我们将使用系统生物学方法将dNaM和蛋白质组数据与现有数据相结合。 通过临床和影像核心。目标4：促进AD生物标记物获取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.