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

摘要

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.