# Mechanisms of exposure-induced tissue functional and pathological changes in a mouse model of Alzheimer's Disease

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $761,561

## Abstract

Exposure to ambient air pollution has been associated with both cognitive impairment and
cardiac dysfunction and a post-mortem study reported evidence of accumulation of
amyloid among people living in cities with high levels of ambient pollution. Whether
exposure to high levels of air pollution accelerates the formation of aggregates is
unknown. We propose a 3 month controlled exposure experiment in Alzheimer’s prone
mice carrying the single mutation in the in the Presenilin-1 gene (PSEN1) (PS1ΔE9) or
the double mutation in the APPswe + the PS1ΔE9 (APPswe/PS1ΔE9). All mice are in the
C57/Bl6J background and C57/Bl6J wild-type mice will serve as controls. Mice will be
exposed beginning at age 3 months to evaluate the impact of concentrated fine particulate
matter (PM2.5) versus filtered air (FA) exposure on brain and cardiac structure and
function. Mice will be studied at two time points: immediately after the exposure and at the
end of the 3-month exposure. Another set of mice will be exposed to PM2.5 for 3 month
than for FA for 3 more months. A control group will be exposed to FA for 6 month. We
hypothesize that Alzheimer’s prone mice exposed to PM2.5 will develop: 1) a greater
quantity of aggregates in the specific anatomical regions of the brain and heart as
assessed by imaging and electron microscopy; 2) worsen brain function assessed with
behavioral studies and cardiac function assessed by echocardiography, biometric
measurements in-vivo and worsen calcium homeostasis in primary neurons and
contractile function and calcium handling in isolated cardiomyocytes in-vitro. We also
hypothesize that exposure to PM will accelerate amyloid pathology by inducing oxidative
stress.

## Key facts

- **NIH application ID:** 9908035
- **Project number:** 5R01AG057046-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Colin K Combs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $761,561
- **Award type:** 5
- **Project period:** 2017-07-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908035

## Citation

> US National Institutes of Health, RePORTER application 9908035, Mechanisms of exposure-induced tissue functional and pathological changes in a mouse model of Alzheimer's Disease (5R01AG057046-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908035. Licensed CC0.

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