Early mid-life environmental toxicant exposures and ad/adrd risk in cardia

Active Cooperative Agreement Awarded Last action

Award ID
U01AG088658
Recipient
Awarding agency
Obligated
$8,607,661

Award facts

Assistance listing
93.866 Aging Research
Completion date 42% complete
Place of performance
Philadelphia, PA 19104, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Alzheimer's disease (ad) and ad-related dementias (adrd) affect more than 6 million americans and 55 million people worldwide. Environmental toxicant exposures from younger age have not been systematically investigated for their roles in ad/adrd risk despite limited suggestive evidence for organochlorine pesticide DDT, organophosphate pesticides, lead, and cadmium. Ad/adrd pathogenesis may take decades to develop before clinical symptoms, thus the role of mid-life exposures on cognitive decline and brain magnetic resonance imaging (MRI) patterns may be critical to examine in identifying preventable environmental risk factors. A crucial mechanism through which these toxicants might act is via epigenetic alterations, alongside processes like neuroinflammation and oxidative stress. There's also a notable racial disparity, with black older adults having a twice as high prevalence of ad as white older adults. This raises questions about the potential interplay between environmental exposures, epigenetic modifications, and social determinants of health (sdoh). In this proposal, we will leverage the ongoing nhlbi-funded coronary artery risk development in young adults (cardia) study to examine the targeted and untargeted exposome and subsequent cognitive decline and brain MRI patterns in this biracial cohort of more than 5,000 black and white young adults at baseline (mean age 25 years) with 35 years of follow-up completed. We will repeatedly measure organochlorine pesticides, polychlorinated biphenyls (pcbs), polybrominated diphenyl ethers (pbdes), untargeted exposome in plasma, and metals and metabolites of organophosphate pesticides in urine samples (aim 1). We will examine exposomic biomarkers for associations with cognitive decline and MRI patterns that increase the ad/adrd risk (aim 2). We will conduct an epigenomic- wide association study to identify epigenomic biomarkers associated with exposomic biomarkers and integrate multi-omic (genomic, epigenomic, transcriptomic, exposomic) data with neuroimaging and cognitive function data to decipher the biological links (aim 3). Finally, we will examine the role of sdoh (including redlining, education, poverty, and discrimination) on the associations between exposomic, epigenomic, and ad/adrd- related cognitive decline and brain MRI patterns (aim 4). This project is highly responsive to the request for application that calls for the quantification of the impact of environmental toxicants on ad/adrd risk in cohort studies, particularly exposure in the mid-age from 30-50 years. The findings will inform the scientific communities and the public about the environmental risk factor of ad/adrd risk, address health disparities among black population, and provide novel exposome data and biological insights for future scientific discoveries.

Transactions

Action Obligated Date
Amendment $2,270,517
Amendment $0
Amendment $0
Amendment $2,081,035
Amendment $2,081,035
Original award $2,175,074

Subawards

Subrecipient Amount Awarded
Northern California Institute For Research And Education, Inc. "Dr. Yaffe and staff will perform the work outlined below: 1. Dr. Yaffe will serve as MPI and PI of the site subcontract with the University of Pennsylvania and… $181,477
Emory University The research at Emory University will be performed in collaboration with Dr. Aimin Chen, Professor with the University of Pennsylvania, PA, to study the effects… $469,500
The University Of North Texas Health Science Center At Fort Worth "Dr. Kai Zhang, PI of the subcontract, will be responsible for the overall performance of the UNTHSC subcontract. Dr. Zhang will work closely with Dr. Aimin… $38,111
Northwestern University "Investigators in the Department of Preventive Medicine at Northwestern University Feinberg School of Medicine in Chicago will work closely with investigators… $534,457
Northern California Institute For Research And Education, Inc. "Dr. Yaffe and staff will perform the work outlined below: 1. Dr. Yaffe will serve as MPI and PI of the site subcontract with the University of Pennsylvania and… $177,694
Emory University The research at Emory University will be performed in collaboration with Dr. Aimin Chen, Professor with the University of Pennsylvania, PA, to study the effects… $460,110
The University Of North Texas Health Science Center At Fort Worth "Dr. Kai Zhang, PI of the subcontract, will be responsible for the overall performance of the UNTHSC subcontract. Dr. Zhang will work closely with Dr. Aimin… $36,483
Northwestern University "Investigators in the Department of Preventive Medicine at Northwestern University Feinberg School of Medicine in Chicago will work closely with investigators… $310,833
The University Of North Texas Health Science Center At Fort Worth "Dr. Kai Zhang, PI of the subcontract, will be responsible for the overall performance of the UNTHSC subcontract. Dr. Zhang will work closely with Dr. Aimin… $34,629
Emory University The research at Emory University will be performed in collaboration with Dr. Aimin Chen, Professor with the University of Pennsylvania, PA, to study the effects… $469,500
Northern California Institute For Research And Education, Inc. Dr. Yaffe and staff will perform the work outlined below: 1. Dr. Yaffe will serve as MPI and PI of the site subcontract with the University of Pennsylvania… $181,165
Northwestern University Investigators in the Department of Preventive Medicine at Northwestern University Feinberg School of Medicine in Chicago will work closely with investigators at… $310,746
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Quick answers

Who received award U01AG088658?

U01AG088658 was awarded to The Trustees Of The University Of Pennsylvania by National Institute on Aging (National Institutes of Health) on September 30, 2024.

How much is award U01AG088658 worth?

$8,607,661 has been obligated on U01AG088658.

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