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Support research that utilizes animal models of LOAD and iPSC-derived cerebral organoids from human donors, to understand the molecular mechanisms by which a variety of exposures (pathogens, toxicants, pollutants) influence the heterogeneity of AD/ADRD.
2025 RFA-AG-24-021: Understanding Gene-Environment Interactions in Brain Aging and Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (U01 Clinical Trial Not Allowed) RFA-AG-24-023: Preclinical Studies to Characterize the Impact of Toxicants on Brain Aging and Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (U01 Clinical Trial Not Allowed) 2.Y Achieved DN 2021 AD Summit: 7.D, 7.L, 7.M and 7.N Blog: Expanding interest in exposome research Research on Disease Mechanisms 2024
- Initiate at least one research program aimed at characterizing the impact of the exposome on the molecular, cellular, physiologic and neuropathologic aspects of AD/ADRD in animal models of LOAD (including polygenic animal models) and identifying surrogate measures of the impact of the exposome on brain aging and AD/ADRD in biosamples that can be obtained non-invasively.
- This research should include studies that utilize systematic perturbation of iPSC-derived cerebral organoids from AD cases and controls, with a range of exogenous factors (i.e., pathogens, toxicants, pollutants, etc.) to characterize the molecular, cellular and neuropathological networks that are perturbed by each factor to enable the detection of shared, as well as distinct mechanism that are associated with different aspects of the exposome.
- Ensure that all data and analytical outputs are made widely available according to open-science and FAIR data practice and encourage the adoption of exposomics-related ontologies for data interoperability.
Summary of Key Accomplishments
Since 2022, NIA has funded an ongoing program that seeks to identify genetic pathways that may render certain individuals more vulnerable to AD/ADRD through exposure to toxic substances present in a shared environment. In 2023, NIA launched a funding opportunity focused on understanding how environmental factors interact with genetic factors in the context of brain aging and AD/ADRD. Projects funded under this initiative will use human cell-based models to study how gene-environment interactions are shaped by exposure to potentially harmful substances encountered in the environment. This new program will be part of NIA’s larger efforts to enable a precision environmental health approach to risk reduction and disease prevention.
The key accomplishments summary is current as of June 2024.