The CSF samples were handled according to the same protocol for quantitative MALDI-FT-ICR MS measurements we reported previously [12] , which consists of a blinded experiment in which the samples were digested by trypsin and subsequently measured by MALDI-FT-ICR (APEX IV Qe 9.6 Tesla MALDI-FT-ICR mass spectrometer (Bruker Daltonics, USA)). After calibration by means of omnipresent albumin peaks, an analysis matrix is generated. A univariate analysis, in which a p-value was determined for every peak position, was used for statistical analysis, in which two groups were compared at a time, for a total of three individual comparisons between the groups. The differentially abundant peaks (p,0.01) in the comparisons were considered for identification purposes. The fold increase of every identified peptide with p,0.01 in the comparisons was determined to confirm differential abundance between groups. Assessment of the statistical background, by means of permutation of a series of 50 scramblings of the samples for each comparison, was used to define a cut-off number for the determination of statistically significant differences between groups. In this permutation procedure all samples are randomly assigned a new group number, scrambling the sample group compositions, prior to performing the univariate analysis to determine the p-values for each peak position. By this method the number of peaks that is assigned a p-value below 0.01 by chance is determined. Iterative repetition of this procedure allows for a statistically relevant mean with standard deviation that could be taken as a realistic background value for this not normally distributed data.