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.

目的：大多数致命性神经退行性疾病肌萎缩性侧索硬化症（ALS）的病因不明。尽管ALS的具体环境病因很大程度上仍是一个谜，但其中一部分病例可能归因于污染物的暴露。某些形式的神经毒性金属汞很容易进入中枢神经系统。鱼不仅是甲基汞的饮食来源，而且还是有益成分，例如omega-3多不饱和脂肪酸。以前使用基于临床的脚趾甲和头发研究作为接触角蛋白生物标志物的先前工作表明，与对照组相比，ALS患者的汞含量升高。我们试图通过美国病例对照比较指甲剪中的汞含量来验证这种关系。方法：我们使用感应耦合等离子体质谱（ICP-MS）对 来自国家ALS生物资源库的n = 70名具有地理代表性的女性ALS患者的指甲剪报进行了痕量元素分析，并将其 与一组中的n = 210名年龄匹配的对照进行比较 来自《姐妹研究》和《两姐妹研究》的n = 1216个全国分布的对照。结果：与指甲汞的最低四分位数相比，中度水平与ALS风险降低相关（P = 4.18e–6）。但是，与对照组相比，ALS患者指甲汞含量高于90％的几率是对照的2.3倍（优势比（OR）= 2.3，95％置信区间1.10-4.58，已根据年龄和吸烟状况进行了调整）。结论：这一发现表明过量的汞暴露可能与衰老人群的神经退行性健康有关。