Metabolomic changes associated with frontotemporal lobar degeneration syndromes.

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Murley, Alexander G  ORCID logo
Jones, P Simon 
Coyle Gilchrist, Ian 
Bowns, Lucy 
Wiggins, Julie 

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.

Corticobasal syndrome, Frontotemporal dementia, Frontotemporal lobar degeneration, Metabolomics, Primary progressive aphasia, Progressive supranuclear palsy, Frontotemporal Dementia, Frontotemporal Lobar Degeneration, Humans, Neurodegenerative Diseases, Supranuclear Palsy, Progressive, Syndrome
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J Neurol
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Springer Science and Business Media LLC
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Wellcome Trust (103838/Z/14/Z)
British Academy (pf160048)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MC_U105597119)
Medical Research Council (MC_UU_00005/12)
This work was supported by the Holt Fellowship, the Wellcome Trust (103838), the Cambridge Centre for Parkinson-plus, the British Academy (PF160048) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme (146281).