Molecular alterations in human olfactory mucosal cells from healthy individuals and individuals with Alzheimer's disease induced by real-world ambient air

Ambient air pollution is a global problem contributing to the development of numerous diseases, including neurodegenerative disorders. Using a mobile exposure system, we investigated the molecular changes in human olfactory cleft mucosal (hOM) cells, a proxy to brain effects, from healthy and Alzheimer's disease (AD) patients modulated by exposure to real-world ambient air. In the samples, exposed at the air-liquid interface (ALI) in a clean, Background locality (very low levels of pollutants) and an Industrial site (air pollution within recommended limits), the production of immune response-related molecules, lipid peroxidation and global RNA expression changes were assessed. The production of leukemia-inhibitory factor (LIF) was increased in the samples from healthy, but not AD individuals in the Industrial locality. No changes in the levels of 15-F2t- isoprostane, a parameter of lipid peroxidation, were detected. When compared with the synthetic air (a blank control) numerous biological processes and KEGG pathways were enriched in the samples exposed in the Industrial, but not the Background locality. In the samples from the healthy subjects, the neurodegenerative disorder-related pathways were significantly affected, indicating the potential of the ambient air to contribute to these diseases. In the AD samples exposed in the Industrial locality, when compared with the Background site, an inflammation-related response was detected, suggesting the potential to exacerbate immune response reactions as a result of ambient air pollution. In summary, our data indicate that exposure to air pollutants, without exceeding the recommended limits, might have significant molecular consequences, potentially contributing to the development of neurodegenerative disorders.