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

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.

Metabolomics of Neurodegenerative Diseases

“…N8-acetyl spermidine increased in individuals with rapidly progressing PD compared to individuals with slow progressing PD. Altered polyamine metabolism in PD Roede et al (2013) Human Plasma LC-ECA 8-Hydroxy-2-deoxyguanosine levels and glutathione significantly increased in PD patients. Uric acid was significantly reduced Bogdanov et al (2008) Human Postmortem CSF LC and GC-mass spec.…”

Recent Advances and Applications of Metabolomics to Investigate Neurodegenerative Diseases

“…PD patients suffer from a very heterogeneous progression of motor degeneration and that variability hampers PD biomarker discovery. In order to find out the biochemical processes responsible for progression velocity and potentially useful biomarkers for PD prognosis, Roede et al (2013) evaluated 100 serum samples (Roede et al, 2013). Serum was obtained from 39 and 41 PD patients with rapid and slow progression, respectively, as well as 20 control subjects.…”

“…Most of the metabolites could not be identified via database matches. Data from high-resolution MS from those unknowns showed matches with numerous phytochemicals, suggesting dietary ingredients might protect against disease development (Roede et al, 2013).…”

“…The barplot (D) shows the mean preservation of adjacency for each of the eigengenes to all other eigengenes; in other words, the barplot depicts the column means of the preservation heatmap. Reprinted with permission from Roede et al (2013). MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin.…”

Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging

“…In a pilot study, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. The 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 [59].…”