Cerebrospinal fluid biomarkers in clinically isolated syndromes and multiple sclerosis

Abstract

A panel of three cerebrospinal fluid (CSF) markers for clinically isolated syndromes (CIS) and multiple sclerosis (MS), based on SDS-PAGE, 2-D maps, and immunoblot results, is here proposed. No individual marker has any specificity, though, since they appear in a number of other neurological diseases. However the set of three, with the respective modulation sign (up-regulated or maintained at constant level), appears to be unique for MS. These proteins are: tau protein (levels remaining constant and undistinguishable from controls, contrary to up- and downregulation in other neurological disorders); 14-3-3 protein (strong upregulation of distinct isoforms) and cystatin C (changing in accordance to disease stage and progression). As an additional evidence, one can rely in the pattern of isoforms of 14-3-3, as obtained by 2-D maps and Western blot analysis: this pattern further distinguishes the variation of this protein from other neurological syndromes, notably sporadic Creutzfeldt-Jakob disease (sCJD), motor neuron diseases and other dementias. In contrast, a similar qualitative and quantitative upregulation of 14-3-3 is observed in Guillain-Barré syndrome (GBS), a demyelinating condition affecting the peripheral nervous system. To the best of our knowledge, this is the first time in which such a panel of biomarkers is reported in MS.