title: Plasma biomarkers associated with ALS and their relationship to iron homeostasis.
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.
authors.affiliation: George M. Leader Family Laboratory, Department of Neurosurgery, Pennsylvania State University College of Medicine, 500 University Drive (H110), Hershey, PA 17033-0850, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Mitchell
authors.forename: Zachary
authors.initials: Z
authors.lastname: Simmons
authors.forename: John L
authors.initials: JL
authors.lastname: Beard
authors.forename: Helen E
authors.initials: HE
authors.lastname: Stephens
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000235:genetics*; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D015415:Biomarkers; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007118:Immunoassay; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D014168:Transferrin / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D005293:Ferritins; D007501:Iron