The Effects of Chronic Exposure to Ambient Traffic-Related Air Pollution on Alzheimer's Disease Phenotypes in Wildtype and Genetically Predisposed Male and Female Rats

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 unc...

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Bibliographic Details
Published in:	Environmental health perspectives 2021-05, Vol.129 (5), p.57005-57005
Main Authors:	Patten, Kelley T, Valenzuela, Anthony E, Wallis, Christopher, Berg, Elizabeth L, Silverman, Jill L, Bein, Keith J, Wexler, Anthony S, Lein, Pamela J
Format:	Article
Language:	eng
Subjects:	Advertising executives Age Aging Air pollution Air Pollution - adverse effects Air Pollution - statistics & numerical data Air quality Air quality standards Alzheimer Disease - genetics Alzheimer's disease Amyloid Animal behavior Animal cognition Animals Brain Cell activation Chronic exposure Cognitive ability Data links Diameters Disease susceptibility Emissions (Pollution) Environmental aspects Epidemiology Exposure Female Females Genetic aspects Genetic Predisposition to Disease Genetics Genotypes Gliosis Health aspects Health risks Hyperspectral imaging Male Males Micrometers Neurodegenerative diseases Neuroimaging Outdoor air quality Particulate emissions Particulate matter Phenotype Phenotypes Pollutants Proteins Rats Risk Risk factors Rodents Sex Tau protein Traffic Traffic flow Traffic-Related Pollution - adverse effects Traffic-Related Pollution - statistics & numerical data Tunnels Ultrafines VOCs Volatile organic compounds
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Summary:	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. This study sought to assess effects of chronic exposure to ambient TRAP on the time to onset and severity of AD phenotypes in a preclinical model and to determine 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 to 14 months to filtered air (FA) or TRAP drawn from the tunnel and delivered to animals unchanged 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 below 24-h PM with aerodynamic diameter less than or equal to 2.5 micrometers ( ) U.S. National Ambient Air Quality Standards limits. Ultrafine PM was a predominant component of TRAP. Nano-sized refractive particles were detected in the hippocampus of TRAP animals. TRAP-exposed animals had more amyloid plaque deposition, higher hyperphosphorylated tau levels, more neuronal cell loss, and greater cognitive deficits in an age-, genotype-, and sex-dependent manner. TRAP-exposed animals also had more microglial cell activation, but not astrogliosis. These data demonstrate that chronic exposure to ambient TRAP promoted AD phenotypes in wildtype and genetically susceptible rats. TRAP effects varied according to age, sex, and genotype, suggesting that AD progression depends on complex interactions between environment and genetics. These findings suggest current regulations are insufficient to protect the aging brain. https://doi.org/10.1289/EHP8905.
ISSN:	0091-6765 1552-9924