The 14-3-3 protein in multiple sclerosis: a marker of disease severity

In multiple sclerosis (MS) axonal damage is an early event and is probably to be considered the most relevant cause of permanent and progressive disability.To investigate the value of the increase of 14-3-3 and tau proteins in the cerebrospinal fluid (CSF) as peripheral markers of axonal pathology and predictors of disease evolution.In the CSF samples obtained from 63 patients with demyelinating diseases (DD), including 20 clinically isolated syndromes (CIS) and 43 clinically defined MS, as well as from 56 controls, we analysed the presence of 14-3-3 reactivity by immunoblot analysis along with the concentration of tau protein by sandwich ELISA.The percentage of DD subjects showing a positive 14-3-3 protein CSF reactivity (38%) was significantly higher than the one previously detected, and was correlated in the MS patients with a more severe clinical phenotype in terms of degree of disability and rate of disease progression, during a 10-month mean clinical follow-up. On the contrary, the levels of the CSF-tau protein were highly variable in DD and control subjects, and the mean CSF-tau concentration was similar in both groups.The immunoblot analysis of 14-3-3 protein in the CSF could be a useful marker to identify a subgroup of DD patients with high risk of developing severe disability.