A Multi-Perspective Transcriptomics Approach to Investigate Alzheimer's Disease and Ultrafine Particles Association

Air pollution is a critical driver of climate change, with significant adverse effects on the global climate. It contributes to the greenhouse effect, alters cloud properties, and impairs the ozone layer. Beyond its environmental impact, air pollution poses serious hazards to human health. Particulate matter (PM), consisting of compounds suspended in the air, is a major component of air pollution. PM, including ultrafine particles (UFPs), can penetrate deep into the lungs and bloodstream upon inhalation, leading to various respiratory and cardiovascular issues. Recent epidemiological studies have linked air pollution exposure to neurological effects, including an increased risk of neurodegenerative diseases such as Alzheimer’s Disease (AD). However, the biological mechanisms underlying this association remain poorly understood. In this context, we explore the potential impact of air pollution, particularly UFP exposure, on Alzheimer’s Disease using a multi-perspective transcriptomics approach based on the olfactory mucosa (OM) tissue. The OM, located at the top of the nasal cavity, serves as a crucial interface between the airways and the brain, making it a promising model for studying neurological disorders. Initially, we analyzed multi-resolution transcriptomics data from OM tissue samples of healthy individuals, AD patients, and Mild Cognitive Impairment (MCI) subjects to identify genetic indicators of neurodegenerative processes. Computational analyses reveal several dementia-related biomarkers, highlighting the OM’s significance in disease research. OM cells from healthy and AD donors were then exposed to vehicle exhausts for 24 and 72 hours to assess the impact of UFP exposure on cellular functions. Our transcriptomics findings demonstrate epithelial barrier damage, altered inflammation processes, and mitochondrial dysfunction in response to UFP exposure, particularly in AD cells. Finally, we develop two R packages, EasyCircR and Stardust, for comprehensive analysis of circular RNAs and spatial transcriptomics data, respectively. Although not yet applied to OM cells, these tools represent innovative approaches that may enhance our understanding of air pollution’s effects on tissue transcriptomics profiles in the future. In conclusion, our research highlights the complex interplay between air pollution and neurodegenerative diseases, laying the foundation for future investigations of the disease environment aimed at developing innovative prevention approaches and treatment strategies.