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

Abstract

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 2.5 μm (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.

Effect of Ethyl Acetate Fraction from Eucommia ulmoides Leaves on PM2.5-Induced Inflammation and Cognitive Dysfunction

“…Also, PM 2.5 exposure increases the activity of poly (ADP-ribose) polymerase (PARP)-1, which promotes the formation of amyloid- β , and shows excessive activity of glial cells as evidence of neuroinflammation [ 64 ]. Exposure to PM 2.5 increased the levels of soluble and insoluble amyloid- β and phosphorylated tau protein in mouse brain tissue [ 65 , 66 ]. In this study, EFEL reduced the expression levels of protein related to inflammatory responses in the lung and brain tissues of mice and decreased the expression levels of amyloid- β and p -tau in the brain tissue.…”

Particulate matter and Alzheimer’s disease: an intimate connection

“…AD is a neurodegenerative (see Glossary) disorder that typically presents in individuals over 65 years old, has a wide variety of symptoms, and is the most common form of dementia [4][5][6][7] (Box 2). Recent studies have found positive correlations between PM exposure and dementia incidence in human cohorts after adjusting for community-and individual-level social and economic characteristics [8][9][10]. Furthermore, mouse models exposed to PM displayed elevated AD biomarkers compared with filtered air (FA) controls [10].…”

“…Recent studies have found positive correlations between PM exposure and dementia incidence in human cohorts after adjusting for community-and individual-level social and economic characteristics [8][9][10]. Furthermore, mouse models exposed to PM displayed elevated AD biomarkers compared with filtered air (FA) controls [10]. Studies have also shown PM exacerbates the aggregation and deposition of the AD hallmarks amyloid beta plaques (Aβ) and neurofibrillary tangles (NFTs) in the brain through mechanisms related to microglia/astrocyte activation, oxidative stress, immune activation, and neuroinflammation [3,[10][11][12][13].…”

“…Furthermore, mouse models exposed to PM displayed elevated AD biomarkers compared with filtered air (FA) controls [10]. Studies have also shown PM exacerbates the aggregation and deposition of the AD hallmarks amyloid beta plaques (Aβ) and neurofibrillary tangles (NFTs) in the brain through mechanisms related to microglia/astrocyte activation, oxidative stress, immune activation, and neuroinflammation [3,[10][11][12][13]. This review presents evidence of neurologic changes induced by PM, with an emphasis on the mechanisms associated with AD pathogenesis.…”