Department of Neurology and Geriatrics, Gifu University, Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
J Neurol Sci. 2011 Apr 15;303(1-2):95-9. doi: 10.1016/j.jns.2011.01.003. Epub 2011 Feb 2.
We measured the levels of some biological metals: copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), and zinc (Zn) in the cerebrospinal fluid (CSF) in patients with neurodegenerative diseases (52 patients with amyotrophic lateral sclerosis (ALS)), 21 patients with Alzheimer's disease (AD), and 20 patients with Parkinson's disease (PD) by inductively coupled plasma mass spectrometry (ICP-MS). The diagnoses were additionally supported by neuroimaging techniques for AD and PD. In ALS, the levels of Mg (p<0.01 significant difference), Fe, Cu (p<0.05), and Zn (p<0.10) in CSF were higher than those in controls. Some patients showed very high levels of Cu and Zn before the critical deterioration of the disease. In AD, the levels of Cu and Zn in CSF were significantly higher in patients with late-onset AD (p<0.01). In PD, we found significantly increased levels of especially Cu and Zn in particular (p<0.01) and Mn (p<0.05) in CSF. A multiple comparison test suggested that the increased level of Mg in ALS and that of Mn in PD were the pathognomonic features. These findings suggest that Cu and Zn in particular play important roles in the onset and/or progression of ALS, AD, and PD. Therefore, Cu-chelating agents and modulators of Cu and Zn such as metallothionein (MT) can be new candidates for the treatment of ALS, AD, and PD.
我们通过电感耦合等离子体质谱法（ICP-MS）测量了神经退行性疾病患者（52 例肌萎缩侧索硬化症（ALS）患者、21 例阿尔茨海默病（AD）患者和 20 例帕金森病（PD）患者）脑脊液（CSF）中的一些生物金属水平：铜（Cu）、铁（Fe）、镁（Mg）、锰（Mn）和锌（Zn）。AD 和 PD 的神经影像学技术进一步支持了这些诊断。在 ALS 中，Mg（p<0.01 有显著差异）、Fe、Cu（p<0.05）和 Zn（p<0.10）在 CSF 中的水平高于对照组。一些患者在疾病恶化之前出现了非常高的 Cu 和 Zn 水平。在 AD 中，晚发性 AD 患者的 CSF 中 Cu 和 Zn 水平显著升高（p<0.01）。在 PD 中，我们发现 CSF 中 Cu 和 Zn 水平明显升高（p<0.01），尤其是 Mn（p<0.05）。多重比较检验表明，ALS 中 Mg 水平升高和 PD 中 Mn 水平升高是其特征性表现。这些发现表明，Cu 和 Zn 尤其在 ALS、AD 和 PD 的发病和/或进展中起重要作用。因此，Cu 螯合剂和 Cu、Zn 调节剂如金属硫蛋白（MT）可以成为治疗 ALS、AD 和 PD 的新候选药物。
