Metal mixtures exposure with risk of elevated serum neurofilament light chain concentrations in U.S. general adults, NHANES 2013-2014.

Background: A relatively well-established link was observed between metal mixtures exposure and neurodegenerative diseases. However, the relationship between metal mixtures exposure and serum neurofilament light chain (sNfL) concentrations, a valuable non-invasive biomarker of neurodegenerative diseases, in general adult populations remains understudied and unclear.

Objective: This study seeks to elucidate the potential impact of metal mixtures exposure on sNfL concentrations in a representative sample of U.S. general adults.

Methods: Twelve urinary metal levels, including barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), antimony (Sb), tin (Sn), strontium (Sr), thallium (Tl), tungsten (W) and uranium (U), were analyzed in U.S. general adults recruited from the 2013-2014 National Health and Nutrition Examination Survey using inductively coupled plasma mass spectrometry (ICP-MS) after a simple dilution step. Urine samples are diluted with 2 % concentrated nitric acid (1:9). We employed a two-pronged approach, combining weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models, to examine the association between the multiple-metals effect and sNfL concentrations. Survey-weighted multivariate linear regression was used to explore the correlation between single-metal effect and sNfL concentrations.

Results: With the increasing quartiles of log-transformed sNfL (log-sNfL) concentrations, the fourth quartile had a higher proportion of smokers and hypertensive individuals (P < 0.001). Cd (69.6 %) and Pb (8.9 %) were the primary drivers of the association between metal mixtures exposure and sNfL concentrations. Analysis of WQS and BKMR models showed a positive association between metal mixtures exposure and sNfL concentrations, especially in older, and male participants.

Conclusion: In the U.S. general adult, a significant correlation between metal mixtures exposure and increased sNfL concentrations was observed, and urinary Cd levels play a pivotal role in this positive correlation. Notably, stronger risk associations were observed among elderly, males, smokers, and hypertensive individuals. The results could be significant for detecting and tracking the beginning of neurodegenerative diseases early, as well as helping to pinpoint individuals at high risk.