Godfrey Michael E, Wojcik Damian P, Krone Cheryl A
Bay of Plenty Environmental Health Clinic, Tauranga, New Zealand.
J Alzheimers Dis. 2003 Jun;5(3):189-95. doi: 10.3233/jad-2003-5303.
Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon (epsilon)4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E epsilon4 groups was found in the patients p<0.001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam. The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3,-dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients. Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.
载脂蛋白E（apo - E）基因分型已被作为对重金属（如铅）神经毒性易感性的一个指标进行研究。此外，apo - Eε4等位基因是神经退行性疾病（包括阿尔茨海默病（AD））的一个主要风险因素。本文讨论了这一风险因素的理论生化基础，并得到了400例疑似汞相关神经精神症状且进行了apo - E测定的患者的数据支持。在这些患者中发现向有风险的apo - Eε4组有统计学意义的偏移（p<0.001）。这些患者平均有13.7颗银汞合金补牙填充物和31.5个银汞合金表面。这远远超过了能产生银汞合金中汞的最大确定可耐受日摄入量的数量。由于症状和体征的非特异性，慢性低水平汞中毒的临床诊断和证实一直很困难。银汞合金是普通人群中汞的最大来源，大脑、血液和尿液中的汞水平随着口腔中银汞合金填充物和表面数量的增加而相应升高。通过用2,3 - 二巯基丙烷磺酸盐（DMPS）激发后测量尿汞，可以确认汞的体内负荷升高，150例患者进行了此项测量。对于那些长期接触汞且有神经病理学（包括AD）风险增加的人，apo - E基因分型作为一种临床有用的生物标志物值得研究。此外，当临床发现提示慢性汞暴露有不良影响时，DMPS尿汞激发试验似乎是一个简单、廉价的程序，能提供客观的确证证据。现在，初级卫生保健从业者可能有机会帮助识别那些风险更大的人，并可能预防随后的神经功能恶化。
