Metabolomic changes associated with frontotemporal lobar degeneration syndromes.
Corticobasal syndrome
Frontotemporal dementia
Frontotemporal lobar degeneration
Metabolomics
Primary progressive aphasia
Progressive supranuclear palsy
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
10
02
2020
accepted:
03
04
2020
revised:
02
04
2020
pubmed:
12
4
2020
medline:
22
6
2021
entrez:
12
4
2020
Statut:
ppublish
Résumé
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. 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. 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). 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.
Identifiants
pubmed: 32277260
doi: 10.1007/s00415-020-09824-1
pii: 10.1007/s00415-020-09824-1
pmc: PMC7359154
mid: EMS86386
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2228-2238Subventions
Organisme : Wellcome Trust
ID : 103838
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105597119
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00005/12
Pays : United Kingdom
Organisme : British Academy
ID : PF160048
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