Metabolomic profiling in multiple sclerosis: insights into biomarkers and pathogenesis.
Metabolomics enables the provision of sensitive bio-markers of disease. We performed 800 MHz (1)H-nuclear magnetic resonance (NMR) spectroscopic analyses of cerebrospinal fluid (CSF) specimens to identify biomarkers of multiple sclerosis (MS), yielding reproducible detection of 15 metabolites from MS (n=15) and non-MS (n=17) patients. Mean levels of choline, myo-inositol and threonate were increased, whereas 3-hydroxybutyrate, citrate, phenylalanine, 2-hydroxyisovalerate and mannose were decreased in MS-derived CSF (p<0.05), suggesting alterations to energy and phospholipid metabolism. Multivariate hierarchal cluster analysis indicated a high correlation within the metabolite profiles, significantly clustering samples into the two clinical groups, which was corroborated using principal components analysis. CSF metabolomics have the capacity to yield quantitative biomarkers and insights into the pathogenesis of MS.
Department of Medicine, University of Alberta, Canada.
S N
SN
Reinke
Department of Medicine, University of Alberta, Canada.
D L
DL
Broadhurst
Department of Biochemistry, University of Alberta, Canada.
B D
BD
Sykes
Department of Psychiatry, University of Alberta, Canada.
G B
GB
Baker
Department of Medicine, University of Alberta, Canada.
I
I
Catz
Department of Medicine, University of Alberta, Canada.
K G
KG
Warren
Department of Medicine, University of Alberta, Canada Department of Psychiatry, University of Alberta, Canada chris.power@ualberta.ca.
C
C
Power
D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D016000:Cluster Analysis; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000401:mortality; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000378:metabolism; D015999:Multivariate Analysis; D010743:Phospholipids / Q000378:metabolism; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D011379:Prognosis; D066244:Proton Magnetic Resonance Spectroscopy
D015415:Biomarkers; D010743:Phospholipids
Multiple sclerosis; biomarker; cerebrospinal fluid; metabolomics; nuclear magnetic resonance