Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project

摘要 AD环境驱动因素特征的暴露组学(EXCEL AD)的目标是提供 研究基础设施，将暴露组学纳入AD/ADRD研究。加里·米勒博士，创始董事 在埃默里大学大力神暴露体研究中心，建立了一个暴露组学实验室 在哥伦比亚大学的CTSA内，并与哥伦比亚阿尔茨海默病研究中心的几名成员合作 中锋(梅尤、泰奇、霍尼格、兰提瓜、斯特恩)。与这些人和其他AD/ADRD调查人员一起在 在哥伦比亚大学，他将促进将暴露组学纳入哥伦比亚大学额外的AD/ADRD研究。在……里面 此外，米勒博士将帮助发展和领导一个由NIA资助的国家AD/ADRD研究小组之间的网络 对暴露组学感兴趣，包括共享方案、方法、分析参考标准、 工作流程和结果，目的是协调AD研究中的暴露数据。我们假设 暴露组学将有助于识别AD的新生物标记物，提供对疾病发病机制的洞察，并确定 在不同种族和民族中观察到的与AD相关的差异的环境因素。Excel AD 我将通过以下目标来检验这一假设。目标1.提高容量、吞吐量和 外源和内源化学特性的鉴定 分辨率质谱学能力。随着我们结合LC/GC分析更多的AD样本 Orbitrap平台上，我们将发现与疾病特征(现有生物标记物、病理学、 影像、临床特征)，需要对未知峰值进行后续识别和表征。这一努力 需要专门的仪器；因此，我们将获得最先进的高分辨率质谱仪 (Thermo IQ-X三联质谱仪)，以帮助识别AD相关特征。目标2.目标 使用非靶向暴露组学和代谢组学为ADRC调查人员执行试点研究 站台。哥伦比亚大学正在进行多项AD/ADRD研究，覆盖了一系列人群 具有不同的种族、疾病阶段和年龄。我们将向哥伦比亚广告公司提供曝光组学方面的咨询 社区，并进行试点研究。此外，我们还将为选定的外部合作伙伴提供分析。穿过 在这一补充中，我们预计将资助六个项目(哥伦比亚大学三个，外部三个)，这些项目有足够的能力产生 发布质量的结果。目标3.通过在线EXCEL AD开发、优化和分发工作流 社区仪表板和其他ADRC和AD研究小组有兴趣将 在他们的研究中暴露了经济学。我们将提供培训、质量控制协议和材料，以及访问 向哥伦比亚以外的AD/ADRD调查人员暴露标准。社区仪表板将编译 并整理正在进行的AD研究的信息，这些研究纳入了暴露组学和其他措施 促进AD的环境因素，包括地理空间分析、基于卫星的遥感和个人 监视器。这将为AD/ADRD暴露组学提供一个智力家园，并促进公平的数据做法。

ABSTRACT The objective of Exposomics for Characterization of Environmental Drivers of AD (EXCEL AD) is to provide the research infrastructure to incorporate exposomics into AD/ADRD research. Dr. Gary Miller, the founding director of the HERCULES Exposome Research Center at Emory University, has established an Exposomics Laboratory within Columbia’s CTSA and collaborated with several members of the Columbia Alzheimer’s Disease Research Center (Mayeux, Teich, Honig, Lantigua, Stern). Together with these and other AD/ADRD investigators at Columbia, he will facilitate the incorporation of exposomics into additional AD/ADRD studies at Columbia. In addition, Dr. Miller will help develop and lead a network among national NIA-funded AD/ADRD research groups interested in exposomics that will include sharing of protocols, methods, analytical reference standards, workflows, and results with a goal of harmonizing exposome data across AD studies. We hypothesize that exposomics will help identify novel biomarkers of AD, provide insight into disease pathogenesis, and identify environmental contributors to the AD-related disparities observed in different races and ethnicities. EXCEL AD will test this hypothesis through the following aims. Aim 1. To improve capacity, throughput, and identification of exogenous and endogenous chemical features through expansion of our high- resolution mass spectrometry capabilities. As we analyze more AD samples with our combined LC/GC Orbitrap platform, we will uncover significant associations with disease traits (existing biomarkers, pathology, imaging, clinical features) that require follow-up identification and characterization of unknown peaks. This effort requires dedicated instrumentation; thus, we will acquire a state-of-the-art high-resolution mass spectrometer (Thermo IQ-X Tribrid Mass Spectrometer) to aid in the identification of AD-associated features. Aim 2. To perform pilot studies for ADRC investigators using the untargeted exposomics and metabolomics platform. There are multiple AD/ADRD studies underway at Columbia University covering a range of populations with diverse ethnicity, disease stage, and age. We will provide consultations on exposomics to the Columbia AD community and perform pilot studies. In addition, we will provide analysis for select external partners. Through this supplement, we anticipate funding six projects (3 at Columbia, 3 outside) of sufficient power to yield publication-quality results. Aim 3. To develop, optimize, and distribute workflows via an online EXCEL AD Community Dashboard among other ADRCs and AD research groups interested in incorporating exposomics into their studies. We will provide training, quality control protocols and materials, and access to exposome standards to AD/ADRD investigators outside of Columbia. The Community Dashboard will compile and curate information on ongoing AD studies that are incorporating exposomics and other measures of environmental contributors to AD, including geospatial analysis, satellite-based remote sensing, and personal monitors. This will provide an intellectual home for AD/ADRD exposomics and promote FAIR data practices.