期刊
JOURNAL OF NEUROCHEMISTRY
卷 158, 期 2, 页码 539-553出版社
WILEY
DOI: 10.1111/jnc.15360
关键词
biomarkers; blood; cerebrospinal fluid; cohort studies; Huntington's disease; Kynurenine
资金
- Medical Research Council [MR/M008592/1, MR/N00373X/1]
- MRC [MR/M008592/1, MR/N00373X/1] Funding Source: UKRI
This study measured KP metabolites in the cerebrospinal fluid and plasma of HD patients and found that these metabolites can be reliably quantified in both biofluids in controls and HD gene expansion carriers. However, the research did not find significant differences in levels of metabolites in patient-derived biofluids and these metabolites were not associated with clinical or imaging measures.
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.
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