Impact-adrd: investigating the multi-omics perturbations associated with complex environmental toxicants and their contribution to alzheimer's disease and related dementias
Active Cooperative Agreement Awarded Last action
- Award ID
- U01AG088425
- Recipient
-
Emory University UEI S352L5PJLMP8
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $9,017,575
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date 44% complete
- Place of performance
- Atlanta, GA 30322, USA
Award details come from USAspending.gov.
Description
- Abstract
- Increased risks of chronic illnesses, including alzheimer's disease and related dementias (ad/adrd), have been linked to exposures to ambient air pollution, particularly fine particulate matter (PM2.5). Despite the observed epidemiological evidence, central and unsolved questions remain on what components of PM2.5 (e.g., sulfate, nitrate, ammonium, elemental carbon, organic carbon, metals, etc.) are most neurotoxic and how they contribute to the observed risk of developing ad/adrd. A better understanding of the specific exposure components and underlying causal biological mechanisms and pathways revealing the link between PM2.5 toxicants and ad/adrd will provide valuable insight into disease etiology and pathophysiology and inform environmental regulation and health policy to reduce disease burden of ad/adrd. Although omics applications in environmental health research are still nascent, several studies conducted by our team and others demonstrate that various single omics approaches, including epigenomics, proteomics, and metabolomics can be used to sensitively map internal biological perturbations following exposures to PM2.5. We propose deeper molecular profiling to investigate the molecular connections underlying the neurotoxicity of individual PM2.5 pollutants and mixtures using high resolution spatio-temporal modeling of PM2.5 components as well as targeted and untargeted profiling of PM2.5 toxicants in blood, cerebrospinal fluid (CSF), and brain tissue. The body's biological response to these toxicants will be determined by measuring perturbations in DNA methylation, proteins, and metabolites in the same tissues. Our study will be based on three well- characterized, diverse cohorts with comprehensive assessment of ad/adrd and related indicators and biomarkers. Participants come from two longitudinal cohort studies prospectively followed at biennial clinical visits and a brain bank from the same study area. They span a wide range of age and cognitive status and reflect the racial diversity of georgia (i.e., 32% african american). Replication of significant findings will be done in the alzheimer's disease neuroimaging initiative (adni). We will 1) characterize individual exposures to chemical and metal components of PM2.5 and determine their impact on ad/adrd risk; 2) elucidate patterns of biological perturbations in single- and multi-omics signatures of the brain associated with PM2.5 toxicants (modelled individually and as mixtures) and how they manifest in CSF and blood of individuals with versus without ad/adrd; and 3) determine the relative contribution of environmental and genetic factors to ad/adrd risk. This study provides a critical opportunity to address research gaps in molecular mechanisms underlying PM2.5 toxicants neurotoxicity and their role in the development of ad/adrd, supporting future efforts that aim to inform environmental regulation and health policy to mitigate air pollution-related risk for ad/adrd. Moreover, IT provides a critical opportunity to enrich deeply phenotyped ad/adrd cohorts with state-of-the-art exposure assessment and omics profiling to understand the environmental impact on ad/adrd.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $109,034 | |
| Amendment | $2,162,957 | |
| Amendment | $0 | |
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| Amendment | $0 | |
| Amendment | $99,867 | |
| Amendment | $99,867 | |
| Amendment | $2,133,773 | |
| Amendment | $2,133,773 | |
| Original award | $2,278,304 |
Show all 15
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Georgia TECH Research Corp | $74,737 | |
| The University Of British Columbia | $99,867 | |
| University Of California, Davis | $112,235 | |
| Georgia TECH Research Corp | $127,792 | |
| The University Of British Columbia | $154,394 | |
| University Of California, Davis | $111,457 | |
| Georgia TECH Research Corp | $117,220 |
Quick answers
Who received award U01AG088425?
U01AG088425 was awarded to Emory University by National Institute on Aging (National Institutes of Health) on August 15, 2024.
How much is award U01AG088425 worth?
$9,017,575 has been obligated on U01AG088425.
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