# Administrative supplement to Endothelial Progenitor Cells and Particulate Air Pollution

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $143,584

## Abstract

ABSTRACT
Improvements in clinical care and the promotion of health life styles have contributed to an aging population,
but one that also increasingly presents with neurological disorders such as Alzheimer's, Parkinson's, dementia,
and cognitive decline in general. While the basis of these outcomes is complex, they likely result from an
interplay of genetic and environmental factors and are biochemically associated with inflammation and
oxidative stress. One environmental factor linked to neurological dysfunction across all age groups is exposure
to fine air borne particulate matter (PM2.5). PM2.5 exposures have been associated with autism spectrum
disorders and learning disabilities in the young and with dementia in older populations. Carnosine is a
naturally-occurring, β-alanine-L-histidine dipeptide found in abundance in skeletal muscle and the brain. It is
thought to promote physiological homeostasis through its ability to sequester hydroxyl radicals and oxidized
lipids, chelate metals, buffer pH, and limit glycation. Given these chemical properties and abundance in the
brain, carnosine has been proposed to limit neurological dysfunction and promote cognition. In this regard,
prior supplementation studies generated inconsistent results or reported limited efficacy, but most of these
studies have used vulnerable populations or had an abbreviated interventional time frame. It remains unclear
therefore, if carnosine supplementation can promote cognition in a generally healthy cohort devoid of
comorbidities. Thus, to test the efficacy of carnosine in promoting cognition and in limiting PM2.5-induced
neurological dysfunction in humans, we will measure cognitive function in participants in the Nucleophilic
Defense Against PM Toxicity (NEAT) trial. In this study, we will enroll participants in the Louisville, KY area
with endogenous carnosine levels that are in the lower third of the normal distribution. Once we have obtained
baseline measures of biomarkers and indices of pre-clinical cardiovascular disease, these participants will be
instructed to take carnosine or placebo supplements for the following 12 weeks, during the summer months
when local PM2.5 levels are at their highest. At two intervals during this time, the participants will return and we
will collect blood and urine samples to assess cardiovascular function, immune responses, and oxidative stress
levels. As outlined in this supplement application, we will also assess cognitive function at baseline and follow
up clinical visits using the validated and highly sensitive Cognition software platform. By enrolling participants
with the lowest endogenous carnosine levels, we will enhance our ability to observe carnosine-mediated
protective effects. Thus, by leveraging the ongoing NEAT study, we will be able to test the additional
hypothesis that dietary carnosine supplementation improves cognitive function in a generally healthy cohort
and mitigates the adverse influences of PM2.5 exposure.

## Key facts

- **NIH application ID:** 10156987
- **Project number:** 3R01ES019217-08S1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Aruni Bhatnagar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $143,584
- **Award type:** 3
- **Project period:** 2011-09-23 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156987

## Citation

> US National Institutes of Health, RePORTER application 10156987, Administrative supplement to Endothelial Progenitor Cells and Particulate Air Pollution (3R01ES019217-08S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10156987. Licensed CC0.

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