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Kynurenine pathway metabolites in cerebrospinal fluid and blood as potential biomarkers in Huntington's disease

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posted on 2021-05-11, 12:10 authored by Filipe B Rodrigues, Lauren M Byrne, Alexander J Lowe, Rosanna Tortelli, Mariette Heins, Gunnar Flik, Eileanoir B Johnson, Enrico De Vita, Rachael I Scahill, Flaviano Giorgini, Edward J Wild
Converging lines of evidence from several models, and post-mortem human brain tissue studies, support the involvement of the kynurenine pathway (KP) in Huntington's disease (HD) pathogenesis. Quantifying KP metabolites in HD biofluids is desirable, both to study pathobiology, and as a potential source of biomarkers to quantify pathway dysfunction and evaluate the biochemical impact of therapeutic interventions targeting its components. In a prospective single-site controlled cohort study with standardised collection of cerebrospinal fluid (CSF), blood, phenotypic and imaging data, we used high-performance liquid-chromatography to measure the levels of KP metabolites - tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid and quinolinic acid - in CSF and plasma of 80 participants (20 healthy controls, 20 premanifest HD, and 40 manifest HD). We investigated short-term stability, intergroup differences, associations with clinical and imaging measures, and derived sample-size calculation for future studies. Overall, KP metabolites in CSF and plasma were stable over 6 weeks, displayed no significant group differences and were not associated with clinical or imaging measures. We conclude that the studied metabolites are readily and reliably quantifiable in both biofluids in controls and HD gene expansion carriers. However, we found little evidence to support a substantial derangement of the KP in HD, at least to the extent that it is reflected by the levels of the metabolites in patient-derived biofluids.

Funding

Medical Research Council. Grant Numbers: MR/M008592/1, MR/N00373X/1

History

Author affiliation

Department of Genetics and Genome Biology

Version

  • VoR (Version of Record)

Published in

Journal of Neurochemistry

Publisher

Wiley

issn

0022-3042

eissn

1471-4159

Acceptance date

2021-03-26

Copyright date

2021

Available date

2021-05-11

Spatial coverage

England

Language

eng

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