Particulate Matter Exposure Exacerbates Amyloid-β Plaque Deposition and Gliosis in APP/PS1 Mice

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (A beta) plaques, neuroinflammation, and neuronal death. There are several well-established genetic and environmental factors hypothesized to contribute to AD progression including air pollution. However, the molecular mechanisms by which air pollution exacerbates AD are unclear. Objective: This study explored the effects of particulate matter exposure on AD-related brain changes using the APP/PS1 transgenic model of disease. Methods: Male C57BL/6;C3H wild type and APP/PS1 mice were exposed to either filtered air (FA) or particulate matter sized under 2.5 mu m (PM2.5) for 6 h/day, 5 days/week for 3 months and brains were collected. Immunohistochemistry for A beta, GFAP, Iba1, and CD68 and western blot analysis for PS1, BACE, APP, GFAP, and Iba1 were performed. A beta ELISAs and cytokine arrays were performed on frozen hippocampal and cortical lysates, respectively. Results: The A beta plaque load was significantly increased in the hippocampus of PM2.5-exposed APP/PS1 mice compared to their respective FA controls. Additionally, in the PM2.5-exposed APP/PS1 group, increased astrocytosis and microgliosis were observed as indicated by elevated GFAP, Iba1, and CD68 immunoreactivities. PM2.5 exposure also led to an elevation in the levels of PS1 and BACE in APP/PS1 mice. The cytokines TNF-alpha, IL-6, IL-1 beta, IFN-gamma, and MIP-3 alpha were also elevated in the cortices of PM2.5-exposed APP/PS1 mice compared to FA controls. Conclusion: Our data suggest that chronic particulate matter exposure exacerbates AD by increasing A beta plaque load, gliosis, and the brain inflammatory status.

Automated summary

This study investigated the effects of particulate matter exposure on AD-related brain changes using a transgenic disease model. The results showed that chronic particulate matter exposure exacerbates AD by increasing A beta plaque load, gliosis, and the brain inflammatory status.