# IMPACT-ADRD: Investigating the Multi-omics Perturbations Associated with Complex Environmental Toxicants and their Contribution to Alzheimer's Disease and Related Dementias

> **NIH NIH U01** · EMORY UNIVERSITY · 2024 · $2,278,304

## Abstract

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...

## Key facts

- **NIH application ID:** 10972892
- **Project number:** 1U01AG088425-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Anke Huels
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,278,304
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10972892

## Citation

> US National Institutes of Health, RePORTER application 10972892, IMPACT-ADRD: Investigating the Multi-omics Perturbations Associated with Complex Environmental Toxicants and their Contribution to Alzheimer's Disease and Related Dementias (1U01AG088425-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10972892. Licensed CC0.

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