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

Feb 8, 2021Journal of Alzheimer's disease : JAD

Air Pollution Increases Amyloid Plaques and Brain Inflammation in Alzheimer’s Model Mice

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Abstract

The Aβ plaque load was significantly increased in the hippocampus of PM2.5-exposed APP/PS1 mice compared to their respective FA controls.

Chronic exposure to particulate matter under 2.5μm may worsen Alzheimer’s disease-related brain changes in a mouse model.
Increased levels of astrocytosis and microgliosis were observed in PM2.5-exposed APP/PS1 mice.
Elevated levels of PS1 and BACE proteins were found in the brains of PM2.5-exposed APP/PS1 mice.
Cytokines associated with inflammation, including TNF-α, IL-6, IL-1β, IFN-γ, and MIP-3α, were increased in the cortices of PM2.5-exposed APP/PS1 mice.

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BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) 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 2.5μm (PM2.5) for 6 h/day, 5 days/week for 3 months and brains were collected. Immunohistochemistry for Aβ, GFAP, Iba1, and CD68 and western blot analysis for PS1, BACE, APP, GFAP, and Iba1 were performed. Aβ ELISAs and cytokine arrays were performed on frozen hippocampal and cortical lysates, respectively.

RESULTS: The Aβ 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-α, IL-6, IL-1β, IFN-γ, and MIP-3α 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 Aβ plaque load, gliosis, and the brain inflammatory status.

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

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