Imbalance of the AKT/MAPK signaling axis mediates the exacerbation of Alzheimer's disease pathology by simulated particulate air pollution from Shihezi in APP/PS1 mice

This study investigated the mechanisms by which a region-specific simulated PM 2.5 from Shihezi, China, exacerbates Alzheimer’s disease (AD) pathology, focusing on the protein kinase B (AKT)/mitogen-activated protein kinase (MAPK) signaling axis. APP/PS1 and wild-type mice were exposed to a simulated Shihezi PM 2.5 suspension. Cognitive function, neuroinflammation, oxidative stress, signaling activity, apoptosis, and amyloid-β (Aβ)/Tau pathology were assessed. Simulated PM 2.5 exposure aggravated cognitive deficits, induced neuroinflammation and oxidative stress, and triggered a significant AKT/MAPK imbalance characterized by MAPK hyperactivation and AKT suppression. This imbalance promoted neuronal apoptosis and exacerbated both Aβ deposition and Tau hyperphosphorylation. Our findings reveal that simulant PM 2.5 -induced neuroinflammation and oxidative stress dysregulate the AKT/MAPK axis, driving neuronal loss and AD progression, and suggest a molecular mechanism by which environmental PM 2.5 exposure may contribute to accelerated neurodegeneration.