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Open Access 01-08-2020 | Frontotemporal Dementia | Original Communication

Metabolomic changes associated with frontotemporal lobar degeneration syndromes

Authors: Alexander G. Murley, P. Simon Jones, Ian Coyle Gilchrist, Lucy Bowns, Julie Wiggins, Kamen A. Tsvetanov, James B. Rowe

Published in: Journal of Neurology | Issue 8/2020

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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Title: Metabolomic changes associated with frontotemporal lobar degeneration syndromes
Authors: Alexander G. Murley
P. Simon Jones
Ian Coyle Gilchrist
Lucy Bowns
Julie Wiggins
Kamen A. Tsvetanov
James B. Rowe
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Frontotemporal Dementia
Frontotemporal Dementia
Aphasia
Progressive Supranuclear Palsy
Published in: Journal of Neurology / Issue 8/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-09824-1

ACC 2024 Congress

Springer Medicine

Metabolomic changes associated with frontotemporal lobar degeneration syndromes

Abstract

Objective

Methods

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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