Background Inflammation and neuronal cell death are involved in HD pathogenesis and biomarkers for these processes could better characterise disease progression and the response to specific interventions.
Aims This exploratory work intended to study general inflammatory cytokines, microglial activation markers, and neuronal cell death markers in the cerebrospinal fluid (CSF) of HD patients.
Methods We assayed CSF TNF-α, IL-1β, IL-6, IL-8, YKL-40, chitotriosidase, tau and NFL from 23 mutation carriers and 14 healthy controls. TNF-α, IL-1β, IL-6, IL-8 and YKL-40 were measured using a MSD antibody-based tetra-plex array with electrochemiluminiscence detection. Chitotriosidase was measured using an in-house enzyme activity assay. Tau and NFL were quantified using commercial ELISAs.
Results TNF-α and IL-1β were below the limit of detection. Mutation carriers had higher YKL-40 (p = 0.003), chitotriasidase (p = 0.015), IL-6 (p = 0.041) and NFL (p = 4.61*10−7) than healthy controls. NFL was different between pre-manifest and manifest mutation carriers (p = 0.006). YKL-40 and NFL showed significant association with age, and YKL-40, IL-8, Tau and NFL displayed significant association with disease burden score. Age-adjusted YKL-40 significantly correlated with disease stage (p = 0.001), TFC score (r = −0.46, p = 0.003), and TMS (r = 0.59, p = 4.32*10−4). TMS remained significant after adjusting for disease burden (r = 0.49, p = 0.028). Age-adjusted NFL significantly correlated with disease stage (p = 6.07*10−5), TFC (r = −0.38, p = 0.005) and TMS (r = 0.47, p = 6.89*10−5).
Conclusions CSF biomarkers of inflammation and neuronal cell death may be useful biomarkers for HD. In particular, YKL-40, IL-8, Tau and NFL may independently predict clinical phenotype and could be useful as biomarkers of disease activity and treatment response. Further investigation is needed to support our exploratory findings.
Funding CHDI Foundation Inc, GSK, Medical Research Council UK, Swedish Research Council and the Wolfson Foundation.
- cerebrospinal fluid
- cell death
- pilot projects