LEAD AND OTHER NEUROTOXINS AS RISK FACTORS FOR AMYOTROPH

工作总结：神经退行性疾病 随着人口老龄化，对公共卫生构成越来越大的挑战。 肌萎缩侧索硬化症是一种神经退行性疾病。 马达系统的。它的病因基本上是未知的，但 暴露在环境神经毒素中可能起到一定作用。我们 进行了一项ALS的病例对照研究，以调查 终生累积接触铅和其他神经毒素， 包括汞、溶剂和杀虫剂。实地工作已完成； 110例肌萎缩侧索硬化症病例，31例临床对照，270例人群对照 都参与了这项研究。我们在三个月内评估了铅暴露 方法：我们使用x射线荧光法测量骨铅 创新的非侵入性技术；我们测量了血铅；我们 组织了一次有组织的面谈，以收集信息 关于潜在的职业、居住和生活方式来源 曝光。迄今为止的研究结果表明，肌萎缩侧索硬化症与 血铅和骨铅水平。与血铅的关系 是出乎意料的，这表明骨铅的新陈代谢可能是 肌萎缩侧索硬化症患者不同。肌萎缩侧索硬化也与 职业性铅暴露，但不包括住宅或 娱乐性曝光。总体而言，这些结果是对之前 研究表明，铅暴露是肌萎缩侧索硬化症的风险因素。我们 还发现肌萎缩侧索硬化症与吸烟有关。进一步 分析将探索肌萎缩侧索硬化症与其他神经毒性的关系 暴露和饮食中的抗氧化剂。此外，两国关系 肌萎缩侧索硬化症的一种常见的基因多态性 三角洲-氨基乙酰丙酸脱水酶的研究探索 进一步探讨肌萎缩侧索硬化症与铅的潜在关系 新陈代谢。

Summary of Work: Neurodegenerative diseases pose an increasing challenge to public health as the population ages. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system. Its etiology is essentially unknown, but exposure to environmental neurotoxins may play a role. We conducted a case-control study of ALS to investigate the effects of cumulative lifetime exposure to lead and other neurotoxins, including mercury, solvents, and pesticides. Field work is complete; 110 ALS cases, 31 clinic controls, and 270 population controls were enrolled in the study. We assessed lead exposure in three ways: we measured bone lead using x-ray fluorescence, an innovative noninvasive technique; we measured blood lead; and we administered a structured in-person interview to gather information on potential occupational, residential, and lifestyle sources of exposure. Results to date show that ALS is strongly associated with both blood and bone lead levels. The relationship with blood lead was unexpected and suggests that metabolism of bone lead may be different in ALS patients. ALS was also associated with occupational exposure to lead, but not with residential or recreational exposures. Overall, these results extend previous studies to suggest that lead exposure is a risk factor for ALS. We also found that ALS was associated with cigarette smoking. Further analyses will explore the relationship of ALS to other neurotoxic exposures and to dietary antioxidants. In addition, the relationship of ALS to a common polymorphism in the gene for delta-aminolevulinic acid dehydratase will be studied to explore further the potential relationship between ALS and lead metabolism.