Ratner Marcia H, Rutchik Jonathan S
Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States.
Neurology, Environmental and Occupational Medicine Associates, CA and Division of Medicine, Occupational Medicine, University of California at San Francisco, San Francisco, CA, United States.
Front Toxicol. 2024 Sep 2;6:1451235. doi: 10.3389/ftox.2024.1451235. eCollection 2024.
There is a well-recognized relationship between a person's body burden of essential trace elements such as copper and their neurological function in which both deficiencies and exposures to excessive concentrations are associated with adverse clinical outcomes. Preclinical studies indicate chronic excess copper exposure is associated with altered motor function, dopaminergic neuronal loss, astrocytosis, and microgliosis. Copper also promotes oligomerization and fibrilization of α-synuclein suggesting it may hasten the course of an α-synucleinopathy. Here we report a rare case of early onset Lewy Body Dementia with Parkinsonism in a 53-year-old Caucasian woman exposed to copper contaminated drinking water for more than 10 years. Her hair and that of her daughter had streaks of blue-green discoloration as did the porcelain sinks in their home. Testing confirmed copper contamination of the drinking water. A neurologist diagnosed her with Lewy Body Dementia with Parkinsonism. Skin biopsy for phosphorylated α was consistent with a diagnosis of an α-synucleinopathy. These findings suggest chronic exposure to excessive copper may act as disease modifying factor in Lewy Body Dementia with Parkinsonism. It has previously been recommended that individuals at risk of Alzheimer's disease (AD) avoid excessive intake of copper. Genetic studies indicate that Lewy Body Dementia shares risk factors and pathways with AD. Based on the observations in this patient we recommend that individuals at risk for an α-synucleinopathy based on a positive family history, genetic testing, and/or positive results on a skin biopsy for phosphorylated α-synuclein avoid exposure to excess copper.
人体必需微量元素（如铜）的体内负荷与其神经功能之间存在一种广为人知的关系，即缺乏和接触过量浓度均与不良临床结果相关。临床前研究表明，长期接触过量铜与运动功能改变、多巴胺能神经元丧失、星形细胞增生和小胶质细胞增生有关。铜还能促进α-突触核蛋白的寡聚化和纤维化，提示其可能加速α-突触核蛋白病的病程。在此，我们报告一例罕见的早发性路易体痴呆伴帕金森综合征病例，患者为一名53岁的白种女性，饮用受铜污染的水超过10年。她和她女儿的头发有蓝绿色条纹，家中的瓷水槽也是如此。检测证实饮用水受到铜污染。神经科医生诊断她患有路易体痴呆伴帕金森综合征。皮肤活检检测磷酸化α-突触核蛋白结果与α-突触核蛋白病的诊断一致。这些发现表明，长期接触过量铜可能是路易体痴呆伴帕金森综合征的疾病修饰因素。此前曾建议有患阿尔茨海默病（AD）风险的个体避免过量摄入铜。基因研究表明，路易体痴呆与AD有共同的风险因素和途径。基于该患者的观察结果，我们建议基于家族史阳性（家族病史阳性）、基因检测和/或皮肤活检检测磷酸化α-突触核蛋白结果呈阳性而有患α-突触核蛋白病风险的个体避免接触过量铜。
