MicroRNA Expression in Asymptomatic Welders: Implications for Biomarker Discovery for Environmentally-Linked Neurodegenerative Disorders

Environmental exposures rarely occur in isolation, yet biomarkers capturing early brain responses to complex metal mixtures remain limited. Neuron-derived miRNAs detectable in peripheral blood may provide minimally invasive indicators of brain-related molecular processes. We profiled miRNAs from neuron-derived extracellular vesicles in 66 adults and identified 50 dysregulated miRNAs. Among these, miR-16-5p, miR-93-5p, and miR-486-5p were reduced in individuals with higher exposure levels. Metal mixture models identified Pb as the metal most consistently associated with these miRNAs. To explore the translational relevance of these findings, we integrated brain MRI measures and observed that mediation analyses suggested miR-16-5p may represent a potential pathway linking Pb exposure to iron-sensitive MRI signals (R2*, a marker of brain iron) in the red nucleus. Together, these results suggest circulating neuron-derived miRNAs may capture molecular signatures linking complex metal mixtures, with Pb as a key component, to neuronal regulatory pathways and early brain-related perturbation to real-world exposures.