The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach
BackgroundSerum 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...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Public Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2025.1516879/full |
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| author | Jiyu Nie Jiyu Nie Lin Wen Zhentian Lai Zhentian Lai Chuhang Lin Chuhang Lin Haiyin Li Haiyin Li Jing Zhang Jing Zhang Shen Xie Shen Xie Xiaosong Ben Chunxia Jing Chunxia Jing |
| author_facet | Jiyu Nie Jiyu Nie Lin Wen Zhentian Lai Zhentian Lai Chuhang Lin Chuhang Lin Haiyin Li Haiyin Li Jing Zhang Jing Zhang Shen Xie Shen Xie Xiaosong Ben Chunxia Jing Chunxia Jing |
| author_sort | Jiyu Nie |
| collection | DOAJ |
| description | BackgroundSerum 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.ObjectiveWe 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.MethodsWe 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.ResultsMultivariate 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).ConclusionThis 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. |
| format | Article |
| id | doaj-art-ee30ec7f56494501bf4d043b857c0476 |
| institution | Kabale University |
| issn | 2296-2565 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Public Health |
| spelling | doaj-art-ee30ec7f56494501bf4d043b857c04762025-08-20T03:31:53ZengFrontiers Media S.A.Frontiers in Public Health2296-25652025-07-011310.3389/fpubh.2025.15168791516879The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approachJiyu Nie0Jiyu Nie1Lin Wen2Zhentian Lai3Zhentian Lai4Chuhang Lin5Chuhang Lin6Haiyin Li7Haiyin Li8Jing Zhang9Jing Zhang10Shen Xie11Shen Xie12Xiaosong Ben13Chunxia Jing14Chunxia Jing15Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, ChinaDepartment of Medical Records, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, ChinaDepartment of Thoracic Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, ChinaBackgroundSerum 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.ObjectiveWe 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.MethodsWe 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.ResultsMultivariate 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).ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fpubh.2025.1516879/fullmetal exposureserum neurofilament light chainunsupervised machine learningBKMRG-computation |
| spellingShingle | Jiyu Nie Jiyu Nie Lin Wen Zhentian Lai Zhentian Lai Chuhang Lin Chuhang Lin Haiyin Li Haiyin Li Jing Zhang Jing Zhang Shen Xie Shen Xie Xiaosong Ben Chunxia Jing Chunxia Jing The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach Frontiers in Public Health metal exposure serum neurofilament light chain unsupervised machine learning BKMR G-computation |
| title | The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach |
| title_full | The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach |
| title_fullStr | The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach |
| title_full_unstemmed | The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach |
| title_short | The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach |
| title_sort | relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general u s population an unsupervised clustering approach |
| topic | metal exposure serum neurofilament light chain unsupervised machine learning BKMR G-computation |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2025.1516879/full |
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