Plasma metabolomic biomarker panel to distinguish patients with amyotrophic lateral sclerosis from disease mimics. Issue 5 (September 2014)

• Record Type: Journal Article
• Authors: Lawton, Kay A.; Brown, Meredith V.; Alexander, Danny; Li, Zhen; Wulff, Jacob E.; Lawson, Robert; Jaffa, Matt; Milburn, Mike V.; Ryals, John A.; Bowser, Robert; Cudkowicz, Merit E.; Berry, James D.; On behalf of the Northeast ALS Consortium
• Is Part Of: Amyotrophic lateral sclerosis and frontotemporal degeneration. Volume 15:Issue 5/6(2014)
• Page Start: 362
• Page End: 370
• Publication Date: 2014-09
• Subjects: 616.839
• DOI: 10.3109/21678421.2014.908311
• Languages: English
• ISSNs: 2167-8421

Abstract

<abstract> <title>Abstract</title> <p>Our objective was to identify plasma biomarkers of ALS that can aid in distinguishing patients with ALS from those with disease mimics. In this multi-center study, plasma samples were collected from 172 patients recently diagnosed with ALS, 50 healthy controls, and 73 neurological disease mimics. Samples were analyzed using metabolomics. Using all identified biochemicals detected in &gt; 50% of all samples in the metabolomics analysis, samples were classified as ALS or mimic with 65% sensitivity and 81% specificity by LASSO analysis (AUC of 0.76). A subset panel of 32 candidate biomarkers classified these diagnosis groups with a specificity of 90%/sensitivity 58% (AUC of 0.81). Creatinine was lower in subjects with lower revised ALS Functional Rating Scale (ALSFRS-R) scores. In conclusion, ALS can be distinguished from neurological disease mimics by global biochemical profiling of plasma samples. Our analysis identified ALS versus mimics with relatively high sensitivity. We identified a subset of 32 metabolites that identify patients with ALS with a high specificity. Interestingly, lower creatinine correlates significantly with a lower ALSFRS-R score. Finally, molecules previously reported to be important in disease pathophysiology, such as urate, are included in our metabolite panel.</p> </abstract>