Keratinous biomarker of mercury exposure associated with amyotrophic lateral sclerosis risk in a nationwide U.S. study

Abstract

Objective: The majority of cases of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are of unknown etiology. A proportion of these cases are likely to be attributable to contaminant exposures, although the specific environmental etiology of ALS remains largely a mystery. Certain forms of the neurotoxic metal mercury readily cross into the central nervous system. Fish is a dietary source of methylmercury, but also of beneficial components, such as omega-3 polyunsaturated fatty acids. Prior work using clinic-based studies of toenails and hair as keratinous biomarkers of exposure suggest elevated mercury levels in ALS patients compared with controls. We sought to validate this relationship in a U.S. case-control comparison of mercury levels in nail clippings. Methods: We performed trace element analysis using inductively coupled plasma mass spectrometry (ICP-MS) on the nail clippings of n = 70 female, geographically representative ALS patients from the National ALS Biorepository and compared them to n = 210 age-matched controls from a set of n = 1216 nationally distributed controls from the Sister and Two Sister Studies. Results: Compared to the lowest quartile of nail mercury, moderate levels were associated with decreased risk of ALS (P = 4.18e–6). However, the odds of having nail mercury levels above the 90th percentile were 2.3-fold higher among ALS patients compared with controls (odds ratio (OR) = 2.3, 95% confidence interval 1.10–4.58, adjusted for age and smoking status). Conclusion: This finding suggests that excessive mercury exposure may be associated with the neurodegenerative health of aging populations.

Keywords:

• Biomarker
• keratin
• nail
• mercury
• amyotrophic lateral sclerosis
• ALS
• U.S.

Acknowledgements

The authors thank the research staff and study participants who made this work possible.

Declaration of interest

The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of ATSDR, CDC, and/or the HHS.

Additional information

Funding

Funding for this study was provided by the Diamond Endowment Project at Dartmouth. The Trace Element Shared Analysis Core is supported by NCI Cancer Center Support Grant 5P30CA023108-37 and NIEHS Superfund grant P42 ES007373. This research was supported in part through the Intramural Research Program of the National Institute of Environmental Health Sciences, NIH, under projects ES103086 and ES044005.