Metabolomic changes associated with frontotemporal lobar degeneration syndromes
Open accessPublished version of a preprint
Abstract
Objective: Widespread metabolic changes are seen in neurodegenerative disease and could be used as biomarkers for diagnosis and disease monitoring. They may also reveal disease mechanisms that could be a target for therapy. In this study we looked for blood-based biomarkers in syndromes associated with frontotemporal lobar degeneration. Methods: Plasma metabolomic profiles were measured from 134 patients with a syndrome associated with frontotemporal lobar degeneration (behavioural variant frontotemporal dementia n = 30, non fluent variant primary progressive aphasia n = 26, progressive supranuclear palsy n = 45, corticobasal syndrome n = 33) and 32 healthy controls. Results: Forty-nine of 842 metabolites were significantly altered in frontotemporal lobar degeneration syndromes (after false-discovery rate correction for multiple comparisons). These were distributed across a wide range of metabolic pathways including amino acids, energy and carbohydrate, cofactor and vitamin, lipid and nucleotide pathways. The metabolomic profile supported classification between frontotemporal lobar degeneration syndromes and controls with high accuracy (88.1–96.6%) while classification accuracy was lower between the frontotemporal lobar degeneration syndromes (72.1–83.3%). One metabolic profile, comprising a range of different pathways, was consistently identified as a feature of each disease versus controls: the degree to which a patient expressed this metabolomic profile was associated with their subsequent survival (hazard ratio 0.74 [0.59–0.93], p = 0.0018). Conclusions: The metabolic changes in FTLD are promising diagnostic and prognostic biomarkers. Further work is required to replicate these findings, examine longitudinal change, and test their utility in differentiating between FTLD syndromes that are pathologically distinct but phenotypically similar.
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Specific metabolic changes were found in bvFTD compared to controls, such as altered metabolites in a wide range of pathways and increased fat preference.
“specific metabolic changes were found in bvFTD (compared to controls), such as altered metabolites in a wide range of pathways (including amino acids, energy and carbohydrate, cofactor and vitamin, lipid and nucleotide) and increased fat preference”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Murley et al., 2020
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- Authors
- Murley, A. G., Jones, P. S., Coyle Gilchrist, I., Bowns, L., Wiggins, J., Tsvetanov, K. A., & Rowe, J. B.
- Affiliations
- University of Cambridge (GB)
- MRC Cognition and Brain Sciences Unit (GB)
- Corresponding author
- Murley, Alexander G.
- Venue
- Journal of Neurology
- Published
- 2020-04-10
- Volume
- 267
- Issue
- 8
- Pages
- 2228-2238
- ISSN
- 0012-1037 (ISSN-L)
- 0340-5354
- 1432-1459
- PMC
- PMC7359154
- OpenAlex
- W3016174158
- Cited by
- 18
- References
- 55
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Neurology (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Apollo
- Funders
- Wellcome Trust (103838)
- Holt Fellowship
- British Academy (PF160048)
- Cambridge Centre for Parkinson plus
- National Institute for Health Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- frontotemporal lobar degeneration, plasma metabolomics, blood-based biomarkers, behavioral variant frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy, corticobasal syndrome, survival prediction, disease classification, neurodegeneration
- MeSH terms
- Humans, Supranuclear Palsy, Progressive, Syndrome, Neurodegenerative Diseases, Frontotemporal Lobar Degeneration, Frontotemporal Dementia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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