Introduction:S100 calcium-binding protein B (S100B) is a biochemical marker of astroglial damage. Purpose: To assess the pathophysiological implications of S100B concentrations in blood plasma and cerebrospinal fluid of patients with neurodegenerative central nervous system disorders. Materials and Methods: In this study, we determined and compare S100B concentrations in blood plasma and cerebrospinal fluid obtained from subjects diagnosed with Alzheimer's disease (n=20), amyotrophic lateral sclerosis (n=12), multiple sclerosis (n=40) and the reference group (n=20), using enzyme-linked immunosorbent assay. Results: Concentrations of S100B in plasma collected from patients diagnosed with Alzheimer's disease (252,38±183,50 pg/mL) and multiple sclerosis (164,92±250,14 pg/mL) were above laboratory standards, but in patients with amyotrophic lateral sclerosis (53,96±56,92 pg/mL) and the reference group (2,12 pg/mL) were below laboratory norms (N>75 pg/mL). Concentrations of S100B in plasma collected from patients with Alzheimer's disease (252,38±183,50 pg/mL) were significantly higher than in patients with amyotrophic lateral sclerosis (53,96±56,92 pg/mL) (pConclusions: Results of our studies indicate the importance of S100B protein concentration assessment in blood in central nervous system disorders differential diagnostics.