# Traffic-Related Emissions Induce Angiotensin II-Dependent Oxidative Stress in the Hippocampus of ApoE-Null Male Mice

## TL;DR

Traffic-related air pollution increases oxidative stress and Alzheimer's disease risk factors in mice lacking ApoE, but this can be reduced with ACE inhibitor treatment.

## Contribution

The study shows TRAP exposure elevates RAS-dependent oxidative stress and amyloidogenic Aβ processing in ApoE−/− mice, which can be mitigated by ACE inhibitors.

## Key findings

- MVE exposure increased plasma Ang II, hippocampal oxidative stress, and inflammation in ApoE−/− mice.
- ACE inhibitor treatment normalized Ang II levels and reduced amyloidogenic markers like APH1B and BACE1.
- TRAP exposure shifts Aβ processing toward amyloidogenic pathways before plaque formation.

## Abstract

Traffic-related air pollution (TRAP) is known to contribute to oxidative stress in the central nervous system (CNS) and has been linked to increased risk of Alzheimer’s disease (AD). Alterations in the renin–angiotensin system (RAS), specifically increased angiotensin II (Ang II) signaling via the angiotensin II type 1 (AT1) receptor, are implicated in increased oxidative stress in the CNS via activation of NADPH oxidase (NOX). As exposure to TRAP may further elevate AD risk, we investigated whether exposure to inhaled mixed gasoline and diesel vehicle emissions (MVE) promotes RAS-dependent expression of factors that contribute to AD pathophysiology in an apolipoprotein E-deficient (ApoE−/−) mouse model. Male ApoE−/− mice (6–8 weeks old) on a high-fat diet were treated with either an ACE inhibitor (captopril, 4 mg/kg/day) or water and exposed to filtered air (FA) or MVE (200 µg PM/m3) for 30 days. MVE exposure elevated plasma Ang II, inflammation, and oxidative stress in the hippocampus, associated with increased levels of Aph-1 homolog B (APH1B), a gamma-secretase subunit, and beta-secretase 1 (BACE1), involved in Aβ production. Each of these endpoints was normalized with ACEi treatment. These findings indicate that TRAP exposure in ApoE−/− mice drives a RAS- and NOX-dependent oxidative and inflammatory response and shifts Aβ processing towards an amyloidogenic profile before overt Aβ deposition, suggesting a potential therapeutic approach for air pollution-induced AD risk.