# Traffic-Related Air Pollutants and Alzheimer's Disease: Risk, Susceptibility and Mechanisms in Women

> **NIH NIH P01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $440,210

## Abstract

Project-1 is designed to investigate the contribution of traffic-related air pollution (TRAP) to the risk,
susceptibility and mechanisms of Alzheimer’s disease (AD) and related dementias (ADRD) in a nationwide
cohort of women from the Women’s Health Initiative (WHI) Memory Studies (WHIMS). ADRD affects more
women than men, and increasing evidence indicates different risk factors by sex, pointing to the need to
identify modifiable environmental factors separately for women and men. In the last two decades, compelling
data have shown that exposure to outdoor air pollutants including TRAP is a novel environmental determinant
of brain aging. Despite the strong evidence for TRAP-induced neurotoxicity (e.g., increased Aβ deposit shown
in Project-3), human data on whether and how TRAP exposure effects brain aging remain limited and
inconsistent. Previous studies had notable limitations: (1) lacking prospective evidence for an increased ADRD
risk associated with TRAP; (2) not based on our current understanding of early cognitive change, biomarkers,
and neurobiological classification of AD; (3) not studying AD risk resulting from TRAP effects before late life
(e.g., aged < 55); and (4) providing limited insight on the brain structure and neuropathology linking TRAP to
early cognitive deficits or an increased risk of AD. To address these knowledge gaps cost-efficiently, Project-1
builds on two well-characterized and geographically-diverse cohorts of mid-aged and older women in the
WHIMS of Younger Women (WHIMS-Y; n=1346, inception age 50-54) and WHIMS-MRI (n=1403, inception
age 65-80) followed annually since 1996, both with comparable longitudinal assessments on episodic memory
and executive function. We further capitalize an NIEHS-funded R01 in WHIMS which employs sophisticated air
pollution models developed by the MESA-Air ("Multi-Ethnic Study of Atherosclerosis and Air Pollution") team to
estimate TRAP (NO2; PM2.5; exposure sources/components). Supported by the Core B1, we take the novel
population neuroimaging approach to studying pathological brain aging in communities, drawing on both
clinical and neuropathological classification of AD defined in very well-characterized samples from the
Alzheimer’s Disease Neuroimaging Initiative with biomarkers of β-amyloid and neuronal injuries. State-of-the-
art mediation and neurocomputational analyses will be conducted to examine the TRAP-affected brain
structures and neuropathological pathways underlying the early cognitive deficits or MRI biomarkers of
increased AD risk. Aim 1 will determine the impact of TRAP on early biomarkers predictive of increased risks
for AD, mild cognitive impairment, and preclinical AD in older women. Aim 2 will examine the associations of
cognitive decline reflecting early AD with TRAP exposure before/during late life. In Aim 3, we will take both
targeted and agnostic approached with high-dimensional neurocomputation to elucidate the brain structure and
neuropathology mediating the ...

## Key facts

- **NIH application ID:** 10456752
- **Project number:** 5P01AG055367-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jiu-Chiuan Chen
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $440,210
- **Award type:** 5
- **Project period:** 2018-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456752

## Citation

> US National Institutes of Health, RePORTER application 10456752, Traffic-Related Air Pollutants and Alzheimer's Disease: Risk, Susceptibility and Mechanisms in Women (5P01AG055367-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456752. Licensed CC0.

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