Pathophysiological implications of actin-free Gc-globulin concentration changes in blood plasma and cerebrospinal fluid collected from patients with Alzheimer's disease and other neurological disorders.

Abstract

The extracellular actin scavenging system (EASS) is composed of plasma Gc-globulin and gelsolin, and is responsible for the elimination of toxic actin from the bloodstream. In this study, we assessed the actin-free Gc-globulin concentrations in blood plasma and cerebrospinal fluid (CSF) obtained from subjects with neurodegenerative and inflammatory diseases of the central nervous system (CNS) as well as in a control group. Using an enzyme-linked immunosorbent assay (ELISA), we measured the actinfree Gc-globulin concentrations in blood plasma and CSF obtained from subjects diagnosed with Alzheimer's disease (AD) (n = 20), amyotrophic lateral sclerosis (ALS) (n = 12), multiple sclerosis (MS) (n = 42), tick-borne encephalitis (TBE) (n = 12), and from a control group (n = 20). The concentrations of free Gc-globulin in plasma collected from patients diagnosed with AD (509.6 ±87.6 mg/L) and ALS (455.5 ±99.8 mg/L) did not differ significantly between each other, but were significantly higher compared to the reference group (311.7 ±87.5 mg/L) (p < 0.001 and p < 0.006, respectively) as well as to MS (310.8 ±66.6 mg/L) (p < 0.001 and p < 0.001, respectively) and TBE (256.7 ±76 mg/L) (p < 0.001 and p < 0.003, respectively). In CSF collected from patients diagnosed with AD and ALS, the concentrations of free Gc-globulin were 2.6 ±1.1 mg/L and 2.7 ±1.9 mg/L, respectively. They did not differ significantly between each other and were significantly higher compared to the reference group (1.5 ±0.9 mg/L) (p < 0.005 and p < 0.041, respectively). Interestingly, in patients with AD, significantly higher values of Gcglobulin were detected compared to multiple sclerosis patients (1.7 ±0.9 mg/L) (p < 0.013). Higher concentrations of free Gc-globulin in blood plasma and CSF collected from patients suffering from neurodegenerative diseases may indicate a potential role of this protein in their pathogenesis, and represent a potential tool for the diagnosis of CNS diseases.