Serum Metabolomics of Slow vs. Rapid Motor Progression Parkinson's Disease: a Pilot Study

• Type of Material: Article
• Authors: James Roede, Emory University; Karan Uppal, Emory University; Youngja Park, Emory University; Kichun Lee, Emory University; Vilinh Tran, Emory University; Douglas Walker, Emory University; Fred Strobel, Emory University; Shannon Rhodes, University of California; Beate Ritz, University of California; Dean P Jones, Emory University
• Language: English
• Date: 2013
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Roede et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0077629
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 10
• Start Page: e77629
• End Page: e77629
• Grant/Funding Information: This work was also supported by a pilot grant from the American Parkinson's Disease Association.; The following research was supported by the grants from the National Institutes of Health and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript: K99ES022266, P01ES016731, R01ES010544, P01ES016732, R01NS038367, U54ES012078.
• Research Categories: Chemistry, General; Chemistry, Physical; Health Sciences, General

Abstract

Progression of Parkinson’s disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.