Metabolomic changes associated with frontotemporal lobar degeneration syndromes

Publication: Journal of Neurology

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

10 April 2020


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 the researchers looked for blood-based biomarkers in syndromes associated with frontotemporal lobar degeneration (FTLD).

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.

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