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Neurochemical biomarkers are urgently sought in ALS. Metabolomic analysis of cerebrospinal fluid (CSF) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy is a highly sensitive method capable of revealing nervous system cellular pathology. The (1)H-NMR CSF metabolomic signature of ALS was sought in a longitudinal cohort. Six-monthly serial collection was performed in ALS patients across a range of clinical sub-types (n = 41) for up to two years, and in healthy controls at a single time-point (n = 14). A multivariate statistical approach, partial least squares discriminant analysis, was used to determine differences between the NMR spectra from patients and controls. Significantly predictive models were found using those patients with at least one year's interval between recruitment and the second sample. Glucose, lactate, citric acid and, unexpectedly, ethanol were the discriminating metabolites elevated in ALS. It is concluded that (1)H-NMR captured the CSF metabolomic signature associated with derangements in cellular energy utilization connected with ALS, and was most prominent in comparisons using patients with longer disease duration. The specific metabolites identified support the concept of a hypercatabolic state, possibly involving mitochondrial dysfunction specifically. Endogenous ethanol in the CSF may be an unrecognized novel marker of neuronal tissue injury in ALS.

Original publication

DOI

10.3109/21678421.2015.1053490

Type

Journal article

Journal

Amyotroph Lateral Scler Frontotemporal Degener

Publication Date

2015

Volume

16

Pages

456 - 463

Keywords

Nuclear magnetic resonance, biomarker, motor neuron disease, neurochemical, proton, Aged, Amyotrophic Lateral Sclerosis, Biomarkers, Case-Control Studies, Citric Acid, Cohort Studies, Discriminant Analysis, Disease Progression, Ethanol, Female, Glucose, Humans, Lactic Acid, Longitudinal Studies, Male, Metabolomics, Middle Aged, Multivariate Analysis, Proton Magnetic Resonance Spectroscopy