# Air pollution, the blood and brain metabolome and their effects on Alzheimer's disease and related dementias

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $807,966

## Abstract

Abstract
Exposures to ambient air pollution, especially fine particulate matter (PM2.5), have been associated with
increased risks of many chronic illnesses, including Alzheimer’s Disease and related dementias (AD/ADRD).
Identification and understanding the role of modifiable risk factors is essential for AD disease prevention.
Despite the observed epidemiological evidence, three central and unsolved questions are 1) what components
of PM2.5 (e.g., sulfate, nitrate, ammonium, elemental carbon, organic carbon, metals, etc.) are most neurotoxic,
2) the role of other ubiquitous air pollutants (carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3))
which often co-occur with PM2.5, and 3) what biological response occurs in the brain following PM2.5 exposure.
A better understanding of the specific exposure components and underlying causal pathways revealing the link
between PM2.5 and AD/ADRD will provide valuable insight into disease etiology and pathophysiology and
inform environmental regulation and health policy to reduce disease burden. Although omics applications in
environmental health research are still nascent, several studies conducted by our team and others
demonstrate that the blood metabolome can be used to sensitively map internal biological perturbations
following exposures to air pollution. The brain and the blood metabolome have also been shown to play an
important role in the development of AD/ADRD. However, most previous studies had limited sample sizes
(N<200), and only focused on associations between PM2.5 and the blood metabolome or on associations
between the metabolome and AD/ADRD markers. No study has looked at these associations with PM2.5 and
AD/ADRD in a cross-tissue analysis of blood and brain to elucidate their interconnections. We propose to
investigate the molecular connections underlying the neurotoxicity of individual and mixtures of air pollutants
using high resolution spatio-temporal modeling of air pollution mixtures, and untargeted cross-tissue
metabolomics approaches in three well-characterized, diverse studies with comprehensive assessment of
AD/ADRD and related indicators and biomarkers. Specifically, we will 1) investigate associations between
exposures to air pollution mixtures and indicators of AD/ADRD, 2) characterize cross-tissue (blood and brain)
metabolomic signatures of air pollution mixtures and indicators of AD/ADRD, and 3) identify early changes in
the blood metabolome as potential biomarkers of the neurotoxicity of exposures to air pollution mixtures by
leveraging prospective assessments of AD/ADRD risk among cognitively normal individuals. This study
provides a critical opportunity to address research gaps in molecular mechanisms underlying air pollution
neurotoxicity and its role in the development of AD/ADRD. These findings will provide key insights into the
relationship between air pollution mixtures, biological response profiles, and ADRD, supporting future efforts
that aim to inform envir...

## Key facts

- **NIH application ID:** 10885577
- **Project number:** 1R01AG087250-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Anke Huels
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $807,966
- **Award type:** 1
- **Project period:** 2024-09-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885577

## Citation

> US National Institutes of Health, RePORTER application 10885577, Air pollution, the blood and brain metabolome and their effects on Alzheimer's disease and related dementias (1R01AG087250-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10885577. Licensed CC0.

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