The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis.
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 wa...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Taylor and Francis
2015
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| _version_ | 1826272506304004096 |
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| author | Gray, E Larkin, J Claridge, T Talbot, K Sibson, N Turner, M |
| author_facet | Gray, E Larkin, J Claridge, T Talbot, K Sibson, N Turner, M |
| author_sort | Gray, E |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:13:38Z |
| format | Journal article |
| id | oxford-uuid:52a90ce3-07c1-4b83-ac3d-f340928754fa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:13:38Z |
| publishDate | 2015 |
| publisher | Taylor and Francis |
| record_format | dspace |
| spelling | oxford-uuid:52a90ce3-07c1-4b83-ac3d-f340928754fa2022-03-26T16:26:48ZThe longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:52a90ce3-07c1-4b83-ac3d-f340928754faEnglishSymplectic Elements at OxfordTaylor and Francis2015Gray, ELarkin, JClaridge, TTalbot, KSibson, NTurner, MNeurochemical 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. |
| spellingShingle | Gray, E Larkin, J Claridge, T Talbot, K Sibson, N Turner, M The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis. |
| title | The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis. |
| title_full | The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis. |
| title_fullStr | The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis. |
| title_full_unstemmed | The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis. |
| title_short | The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis. |
| title_sort | longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis |
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