title: Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics.
abstract: Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS). However, those studies utilized small numbers of ALS and control subjects. Additional studies using larger subject cohorts are required to verify these candidate biomarkers. Cerebrospinal fluid (CSF) samples from 100 patients with ALS, 100 disease control, and 41 healthy control subjects were examined by mass spectrometry. Sixty-one mass spectral peaks exhibited altered levels between ALS and controls. Mass peaks for cystatin C and transthyretin were reduced in ALS, whereas mass peaks for posttranslational modified transthyretin and C-reactive protein (CRP) were increased. CRP levels were 5.84 +/- 1.01 ng/ml for controls and 11.24 +/- 1.52 ng/ml for ALS subjects, as determined by enzyme-linked immunoassay. This study verified prior mass spectrometry results for cystatin C and transthyretin in ALS. CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb-onset disease. Our biomarker panel predicted ALS with an overall accuracy of 82%.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, BST S-420, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ryberg
authors.forename: Jiyan
authors.initials: J
authors.lastname: An
authors.forename: Samuel
authors.initials: S
authors.lastname: Darko
authors.forename: Jonathan Llyle
authors.initials: JL
authors.lastname: Lustgarten
authors.forename: Matt
authors.initials: M
authors.lastname: Jaffa
authors.forename: Vanathi
authors.initials: V
authors.lastname: Gopalakrishnan
authors.forename: David
authors.initials: D
authors.lastname: Lacomis
authors.forename: Merit
authors.initials: M
authors.lastname: Cudkowicz
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000134:cerebrospinal fluid; D055316:Cystatin C / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011228:Prealbumin / Q000032:analysis / Q000378:metabolism; D040901:Proteomics; D013534:Survival
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D007202:Indicators and Reagents; D011228:Prealbumin; D002097:C-Reactive Protein