Plasma biomarkers associated with ALS and their relationship to iron homeostasis

George M. Leader Family Laboratory, Department of Neurosurgery, Pennsylvania State University College of Medicine, 500 University Drive (H110), Hershey, PA 17033-0850, USA.
Muscle & Nerve (Impact Factor: 2.31). 07/2010; 42(1):95-103. DOI: 10.1002/mus.21625
Source: PubMed

ABSTRACT Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis with variable presentation and disease progression. There is a critical need for a panel of biomarkers to provide clinicians and researchers with additional information. In this study, multiplex immunoassays were used to screen a number of cytokines, growth factors, and iron-related proteins. ALS patients had significantly higher plasma levels of L-ferritin and lower concentrations of transferrin when compared to healthy controls and together classified a test group of subjects with 82% accuracy. Duration of ALS symptoms correlated positively with levels of monocyte chemoattractant protein 1 (MCP-1) and negatively with levels of granulocyte-macrophage colony stimulating factor (GM-CSF). The biomarker profile suggests iron homeostasis is disrupted in ALS patients, and changes in ferritin and transferrin (Tf) appear to be indicators of ongoing inflammatory processes. The data demonstrate a plasma biomarker profile in ALS patients that may differ from published reports of cerebrospinal fluid biomarkers.

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    • "High levels of high mobility group box 1 (HMGB1) autoantibody (Hwang et al., 2013), increased granzyme B (Ilzecka, 2011), higher CSF IL-8 levels (Mitchell et al., 2009) and wide-range C-reactive protein (wrCRP) (Keizman et al., 2009) correlated with disease severity as measured by ALSFRS-R. In addition, increased levels of blood MCP-1, TNF-α and GM-CSF correlated with disease duration (Kuhle et al., 2009; Mitchell et al., 2010). Two glial-derived proteins, sCD14 (a soluble monocyte receptor involved in inflammation in neurodegenerative diseases) and S100B (an astrocyte-derived neurotrophic protein) show decreased levels in CSF of patients with ALS (Sussmuth et al., 2003, 2010). "
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