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Emulating Chronic Near-Roadway Exposures for Studying Alzheimer's Disease
KEITH BEIN, Kelley Patten, Anthony Valenzuela, Christopher Wallis, Elizabeth Berg, Jill Silverman, Anthony S. Wexler, Pamela Lein, University of California, Davis
Abstract Number: 669
Working Group: Aerosol Exposure
Abstract
Epidemiological data link traffic-related air pollution (TRAP) to increased risk of Alzheimer’s disease (AD). Preclinical data corroborating this association are largely from studies of male animals exposed acutely or subchronically to high levels of isolated fractions of TRAP. What remains unclear is whether chronic exposure to ambient TRAP modifies AD risk and the influence of sex on this interaction. Our study assesses the effects of chronic exposure to ambient TRAP on the time to onset and severity of AD phenotypes in a pre-clinical model and whether sex or genetic susceptibility influences outcomes. Male and female TgF344-AD rats that express human AD risk genes and wildtype littermates were housed in a vivarium adjacent to a heavily trafficked tunnel in Northern California and exposed for up to14 months to filtered air (FA) or TRAP drawn from the tunnel and delivered to animals unaltered in real-time. Refractive particles in the brain and AD phenotypes were quantified in 3-, 6-, 10-, and 15-month-old animals using hyperspectral imaging, behavioral testing, and neuropathologic measures. Particulate matter (PM) concentrations in TRAP exposure chambers fluctuated with traffic flow but remained well below 24-hr PM2.5 National Ambient Air Quality Standards. Results show that (1) ultrafine PM was the predominant component of TRAP, (2) nano-sized refractive particles were detected in the hippocampus of TRAP animals., (3) TRAP-exposed animals had more amyloid plaque deposition, higher hyperphosphorylated tau levels, more neuronal cell loss, increased microglial cell activation, and greater cognitive deficits in an age-, genotype-, and sex- dependent manner. These data suggest that AD progression depends on complex interactions between environment and genetics and that current PM2.5 regulations are insufficient to protect the aging brain. Results will be presented in combination with a comprehensive characterization of exposure dynamics at the tunnel facility.