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Comparing effects of gaseous vs. particulate components of traffic-related air pollution on Alzheimer’s disease biomarkers in a genetically susceptible rat model

Nasim, Nathifa1; Cheng, Mei-Yun1; Park, Heui Hye1; Valenzuela, Anthony1; Andrew, Peter1; Wexler, Anthony1; Chandrasekaran, Vidya2; Van Winkle, Laura1; Bein, Keith1; Lein, Pamela1

Published Jun 10, 2026 on Dryad. https://doi.org/10.5061/dryad.0gb5mkmgk

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Abstract

This study assesses the effects of gas phase vs. particulate matter (PM) components of traffic related air pollution (TRAP) from light-duty only (LDV) vs. mixtures of light- and heavy-duty vehicles (LDV+HDV) on Alzheimer's disease (AD)-relevant pathology as well as sex-by-exposure interactions in a transgenic rat model of AD. Male and female TgF344-AD rats were exposed starting at 1 month of age and randomly assigned to one of six exposure groups: (1) filtered air (FA), (2) LDV+HDV gases only; (3) LDV PM only; (4) LDV+HDV PM only; (5) LDV PM and gases; and (6) LDV+HDV PM and gases. AD-relevant endpoints were quantified in 4-, 9-, 12-, and 15- month-old animals. Cortical Aβ levels were assessed using ELISA, and quantitative immunohistochemistry (qIHC) was used to assess spatiotemporal progression of amyloid fibrils (OC antibody), density of neurons (NeuN), phosphorylated tau, and staining via thioflavinS to quantify amyloid plaques and neurofibrillary tangles. qIHC was separated by region: hippocampal dentate gyrus (DG), CA1, CA3, and entorhinal cortex (EC). Cortical Aβ levels were observed to have significant sex-by-exposure interactions and sex-dependent effects on amyloid plaque accumulation were also observed. Both sexes exhibited increased plaque levels at 15 months of age in the entorhinal cortices of rats exposed to PM alone or with LDV gases; females exposed to PM from LDV+HDV emissions had increased plaques in the hippocampus at the 9-month timepoint. The rate of plaque accumulation over all four time points was accelerated in the entorhinal cortices of both sexes exposed to PM alone, and in combination with gases, from both LDV and LDV+HDV emissions. There were no exposure effects on neuronal count, phosphorylated tau (pTau), and ThioS+ proteinopathy. TRAP effects varied according to age, sex, and brain region, suggesting that complex gene x environment interactions dictate the development of AD-related phenotypes. Further research is needed to determine the mechanisms by which the interaction of sex and TRAP may be influencing the aging brain so that effective interventions can be developed.