Particulate Matter Exposure and Alzheimer's Disease: In Vivo Insights into Neurotoxic Mechanisms

JOSEPH V. PUTHUSSERY, Yuezhi (August) Li, Shu-Wen You, Clare Wallace, Jessica Restivo, Carla M. Yuede, Rajan K. Chakrabarty, John Cirrito, Washington University in St. Louis

     Abstract Number: 510
     Working Group: Health-Related Aerosols

Abstract
A growing body of epidemiological research identifies ambient particulate matter (PM) as a potential neurotoxin linked with the onset of Alzheimer's disease (AD). Researchers hypothesize that the chemical components present in PM, such as transition metals and carbonaceous aerosols if exposed to the brain, can induce chronic inflammation and produce reactive oxygen species that can damage the blood-brain barrier and increase the production of amyloid-beta (Aβ; a biomarker of AD) peptides. While there is compelling evidence of a plausible association between air pollution exposure and AD, the exact mechanism of PM-induced neurotoxicity and AD remains largely unknown. Previous studies in AD mouse models have focused on the effects of long-term exposure to air pollution, but the immediate changes in brain activity during acute PM exposure have been technologically challenging to monitor.

In response, we have developed a whole-body mouse exposure chamber integrated with an in vivo microdialysis (MD)-based system for real-time measurement of brain interstitial fluid (ISF) Aβ peptide levels. This setup comprises a state-of-the-art in situ measurement technique and houses two mice in individual RaTurn cages designed for movement and ad-lib access to food and water. Microdialysis probes, implanted in the mice's hippocampus, allow for continuous ISF sampling in awake, freely moving mice at 60-minute intervals over three days. Our findings show that Aβ levels vary significantly with the type of pollutant; low volatility organic aerosols (LVOA) induce a sharp increase in Aβ peptides (~100%) shortly after two-hour exposure. Ongoing experiments aim to dissect the mechanisms behind these changes by investigating oxidative stress markers and reactive oxygen species generation in response to various pollutants through a combination of in vivo and in vitro studies.