Journal
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
Volume 16, Issue 7-8, Pages 456-463Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/21678421.2015.1053490
Keywords
Nuclear magnetic resonance; proton; motor neuron disease; neurochemical; biomarker
Categories
Funding
- Motor Neurone Disease Association UK Care Centre Funding Programme
- Thierry Latran Foundation
- Medical Research Council & Motor Neurone Disease Association UK Lady Edith Wolfson Senior Clinical Fellowship
- Cancer Research UK [16945] Funding Source: researchfish
- Medical Research Council [G0701923, MR/K01014X/1] Funding Source: researchfish
- Motor Neurone Disease Association [Turner/Jan13/944-795] Funding Source: researchfish
- MRC [G0701923, MR/K01014X/1] Funding Source: UKRI
Ask authors/readers for more resources
Neurochemical biomarkers are urgently sought in ALS. Metabolomic analysis of cerebrospinal fluid (CSF) using proton nuclear magnetic resonance (H-1-NMR) spectroscopy is a highly sensitive method capable of revealing nervous system cellular pathology. The H-1-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 H-1-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available