Review on metal speciation analysis in cerebrospinal fluid-current methods and results: a review

The large number of patients suffering from neurodegenerative diseases like Alzheimer's disease and Parkinson's disease motivates many research groups worldwide to investigate pathogenic factors and molecular mechanisms of these diseases. Recent studies and reviews indicate that metals are involved in these neurodegenerative processes in case their homeostasis in the brain is disturbed. Important is that the focus of these recent studies is on essential metals like Fe, Cu, Zn and Mn, but not on the well-known neurotoxic metals like Hg and Pb. Key issues for understanding metal induced neurotoxic effects are the transport processes across the neural barriers, the metal binding forms (species) and their interactions with neuronal structures. Total metal concentrations in cerebrospinal fluid were published in several studies for controls and patients, but the amount of reliable data sets is not yet sufficient for clear definition of normal and elevated levels. The need for more detailed information on metal species in CSF is highlighted in this review. However, studies on element speciation analysis, that means identification and quantification of the various binding forms of metals in cerebrospinal fluid, are rare. The major reasons therefore are difficulties in accessing cerebrospinal fluid samples, the non-covalent nature of many metal species of interest and their rather low concentrations. In spite of this, several applications demonstrate the potential of hyphenated techniques as additional diagnostic tools for cerebrospinal fluid analysis. This review shows the importance of trace element analysis and more specifically of element speciation in cerebrospinal fluid for an improved understanding of pathologic mechanisms promoting neuro-degeneration. Respective analytical techniques are also highlighted. Additionally, biochemical assays for selected high molecular mass metal species are summarized and critically discussed. Moreover additional potential techniques like direct non-invasive methods as well as mathematical modelling approaches are considered. Data on total concentrations of numerous elements in CSF as well as speciation information of elements such as Al, As, Ca, Cd, Cu, Fe, Mg, Mn, Hg, Pb, Se and Zn in CSF are summarized.