ORIGINAL RESEARCH article
Front. Public Health
Sec. Environmental Health and Exposome
Volume 13 - 2025 | doi: 10.3389/fpubh.2025.1516879
Number of words:3816 Number of figures:8 Number of tables:2 The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach
Provisionally accepted
Jiyu Nie1Lin Wen1,2Zhentian Lai1Chuhang Lin1Haiyin Li1Jin Zhang1Shen Xie1Xiaosong Ben2
CHUNXIA JING1*- 1School of Medicine, Jinan University, Guangzhou, China
- 2Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China
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Background: Serum neurofilament light chain (sNfL) has demonstrate significant clinical value in quantifying neuronal injury. Concurrently, extensive evidence has linked metal exposure to neurotoxic effects. However, the potential association between metal exposure and circulating sNfL levels remains uninvestigated in population-based study.Objective: We applied a novel unsupervised clustering method (k-medoids) incorporating blood metals concentrations to stratify the general U.S. population into different exposure profiles to investigate the association between metal exposure and sNfL levels.Methods: We analyzed data from the 2013-2014 NHANES cycle, and 513 participants were included in this study. Multivariate regression model, Bayesian kernel regression (BKMR) and quantile g-computation (QGC) were used to assess the relationship between individual and mixed metal exposure and sNfL. Results: Multivariate regression revealed a significant positive association between blood cadmium concentrations and elevated sNfL levels in the overall population (β = 0.115, 95%CI: 0.039-0.190, p = 0.003). Through exposure pattern recognition using unsupervised k-medoids clustering, participants were stratified into distinct exposure subgroups: a high-exposure cluster (n=326) and a low-exposure (n=187) reference group. BKMR modeling within the high-exposure group identified cadmium as the dominant contributor to sNfL elevation, with stronger effects in male participants (β = 0.201, 95%CI: 0.087-0.315) and individuals with BMI >25 kg/m2 (β = 0.178, 95%CI: 0.062-0.294).Conclusions: This study provides systematic evidence that blood cadmium concentration can be used as the predominant driver of early neuronal injury, as objectively quantified through sNfL biomarker.
Keywords: Metal exposure, Serum neurofilament light chain (NfL), Unsupervised machine learning, BKMR, G-computation (QGC)
Received: 25 Oct 2024; Accepted: 30 Jun 2025.
Copyright: © 2025 Nie, Wen, Lai, Lin, Li, Zhang, Xie, Ben and JING. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: CHUNXIA JING, School of Medicine, Jinan University, Guangzhou, China
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