Journal of hazardous materialsJun 10, 2025

Microglia cell particles may cause air pollution-linked Alzheimer's-like behaviors through a specific molecular pathway

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 3, 2026

Abstract

PM2.5 exposure drives microglial cells toward a pro-inflammatory state, impairing brain immune defenses.

Long-term exposure to fine particulate matter (PM2.5) is associated with neurological disorders, including Alzheimer's disease.
Microglia exposed to PM2.5 secrete extracellular vesicles (EVs) enriched with miR-34a-5p.
These EVs target the DUSP10 protein in neurons, activating the p-p38 MAPK pathway.
Activation of this pathway leads to increased tau phosphorylation and accumulation of pathological amyloid-beta (Aβ) proteins.
The resulting changes induce neuronal cell death in the hippocampus and cortical regions.
Knocking down miR-34a-5p in EVs from PM2.5-treated microglia may rescue cognitive and behavioral deficits in mice.

Simplified

Fine particulate matter (PM2.5), a major component of air pollution, poses significant global health risks. Epidemiological studies have correlated long-term PM2.5 exposure and neurological disorders, including Alzheimer's disease (AD). Extracellular vesicles (EVs) are recognized as critical mediators of intercellular communication. Understanding the role of microglia EVs in neuronal dysfunction is essential, given the increasing awareness of non-cell-autonomous neurotoxicity. The mechanisms through which microglia and their EVs mediate PM2.5-induced neurotoxicity are poorly understood. This study demonstrated that PM2.5 exposure drives microglial toward the pro-inflammatory M1 phenotype, impairing the brain's immune defenses. PM2.5-treated microglia secrete miR-34a-5p-enriched EVs. These EVs are delivered to neurons, target DUSP10, activate the p-p38 MAPK pathway, increase aberrant tau phosphorylation and pathological Aβ proteins, and induce neuronal apoptosis in the hippocampus and cortical regions. These pathological changes contribute to cognitive and behavioral deficits in PM2.5-exposed mice. Knocking down miR-34a-5p in EVs from PM2.5-treated microglia rescued these phenotypes, mitigating AD-like pathology in mice. Our study identified miR-34a-5p as a critical regulator of neuro apoptosis and AD-like cognitive impairment induced by PM2.5 exposure. These findings underscore the pivotal role of microglial EVs in mediating intercellular communication between glia and neurons, providing valuable insights into the mechanisms underlying PM2.5-induced neurotoxicity.

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Microglia cell particles may cause air pollution-linked Alzheimer's-like behaviors through a specific molecular pathway

Abstract

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