Patterns of levels of biological metals in CSF differ among neurodegenerative diseases

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / pathology
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid
  • Amyotrophic Lateral Sclerosis / pathology
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Mass Spectrometry
  • Metals / cerebrospinal fluid*
  • Metals, Heavy / cerebrospinal fluid
  • Middle Aged
  • Neurodegenerative Diseases / cerebrospinal fluid*
  • Neurodegenerative Diseases / pathology
  • Parkinson Disease / cerebrospinal fluid
  • Parkinson Disease / pathology


  • Metals
  • Metals, Heavy