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

Chronic occupational exposure to metals in welding fumes has been implicated in the etiology of neurodegenerative diseases (NDDs), including Parkinson's disease (PD) and Alzheimer's disease (AD). Changes in microRNA (miRNA) expression have been associated with various neurodegenerative conditions. Circulating miRNAs, in particular, have emerged as promising, minimally invasive biomarkers for diagnosing and monitoring disease progression. This study was designed to characterize the expression of miRNAs in neuronally-enriched serum extracellular vesicles (EVs) among welders and non-welders to explore their potential link to metal concentrations and welding exposure measures and their potential as early diagnostic biomarkers for neurodegeneration. Serum samples from 39 welders and 27 healthy individuals were collected, and EV-enclosed miRNAs were extracted and analyzed. Also, whole blood metal concentrations and welding exposure measurements were obtained. Fifty miRNAs were found to be dysregulated in welders vs. non-welders, of which three (miR-16-5p, miR-93-5p, miR-486-5p) showing reduced expression and two (miR-4281 and miR-4417) exhibiting positive correlations with blood metal concentrations as well as with long- and short-term welding exposure measures. The dysregulation of these miRNAs suggests that exposure to metals could disrupt important biological processes, possibly contributing to an elevated risk of NDDs. These findings highlight the need for further research to validate the causal relationship between exposure to metals in welding fumes, the dysregulation of circulating miRNAs, and their role in neurodegenerative disease development, with implications for miRNA-based biomarkers in early disease detection and prevention.