1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis.
BACKGROUND
Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by (1)H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS.


METHODS
CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional (1)H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses.


RESULTS
Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites revealed that patients were accurately classified 81.6% of the time.


CONCLUSIONS
CSF screening by NMR spectroscopy could be a useful, simple and low cost tool to improve the early diagnosis of ALS. The results indicate a perturbation of glucose metabolism, and the need to further explore cerebral energetic metabolism.
Inserm U930, CNRS 2448, Tours, France. helene.blasco@univ-tours.fr
Hélène
H
Blasco
Philippe
P
Corcia
Caroline
C
Moreau
Ségolène
S
Veau
Clémentine
C
Fournier
Patrick
P
Vourc'h
Patrick
P
Emond
Paul
P
Gordon
Pierre-François
PF
Pradat
Julien
J
Praline
David
D
Devos
Lydie
L
Nadal-Desbarats
Christian R
CR
Andres
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid*; D001205:Ascorbic Acid / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D025341:Principal Component Analysis; D011522:Protons; D011773:Pyruvates / Q000134:cerebrospinal fluid
D011522:Protons; D011773:Pyruvates; D001205:Ascorbic Acid