Aldehyde exposure induces axonal damage through inflammatory response

Abstract The potential neurological effects of low-concentration aldehydes in the human body remain largely unexplored. To address this, we conducted a study involving 331 participants from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. Utilizing logistic regression model, bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression models, we examined the combined impact of serum aldehydes on the overall risk of axonal damage. Through bioinformatics and mediation analyses, we unraveled the mechanisms underlying aldehyde-induced axonal damage. In our logistic regression model, we found associations between isopentanaldehyde and hexanaldehyde with neurofilament light chain (NfL) levels (fourth vs. first quartile). BKMR analysis demonstrated a significant overall effect of aldehydes on NfL levels when all chemicals were at or above the 55th percentile, compared to the 50th percentile. Additionally, WQS regression analysis revealed a positive association between the WQS index and NfL concentrations(OR = 2.46, 95%CI: 1.27–4.73). In terms of pathways and hub genes, inflammatory response and TNF emerged as the top-ranking enrichment pathway and hub gene. Notably, mediation analysis indicated that WBC, MONO, and NEUT played significant roles in mediating the relationships between isopentanaldehyde and NfL concentrations. Collectively, the current evidence suggests that aldehyde exposure may elevate the risk of axonal damage through inflammatory response.