The target of early and efficient treatment in patients with multiple sclerosis (MS)is hampered by a lack of prognostic biomarkers that can predict disease progression, severity, and responses to treatment. The scope of the study is to evaluateneuron cytoskeletal and astroglial biomarkers in the cerebrospinal fluid (CSF) and serum(tau, phospho-tau and glial fibrillary acidic protein(GFAP) and correlate with clinical characteristics of MS patients. 87 MS patients (aged 41.1+-11.96) enrolled in the study and 21 controls (aged 44.17 +-12.8). The female/male ratio was 8 females/12males in the controls and 64 females/20males in the patients’ group. From the patients’ cohort 86% (75 patients) were relapsing forms and 14% (12 patients) were progressive forms of the disease. From the total sample 60 patients had disease duration more than a year and 48 less or equal to 1 year. CSF levels of b-amyloid, tau, phospho tau and GFAP were determined using enzyme-linked immunosorbent assay. A significant difference was evident in the levels of phospho tau181 in the CSF of patients (p=0.03) with phospho tau median 34.5 (INQ 22-89) in the relapsing groups and phospho tau median 40.4 (INQ 26-267) in the progressive one. In a linear regression model a potential association was revealed between GFAP serum and Expanded Disability Status Scale change from baseline, with a negative association between GFAP serum levels and EDSS change (b=-2.95;95%CI:from-4.58to-1.32;p=0.003), adjusting for age. EDSS score showed correlation with age (ρ=0.26, p=0.005). Phospho tau proved the most important biomarker to discriminate between relapsing and progressive forms on multiple sclerosis patients. More studies are needed to validate the results, but our study provides preliminary evidence of CSF phopsho t as potential end point surrogate biomarker of progressive MS, GFAP serum as a potential biomarker of relapse.