Objective: 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.

Background: Inflammation and cell death are involved in HD pathogenesis and biomarkers for this processes could be relevant to better characterise the therapeutic response to specific interventions.

Methods: We essayed CSF TNF-α, IL-1β, IL-6, IL-8, YKL-40, chitotriosidase, total tau and neurofilament light chain (NfL) from 23 mutation carriers, of whom 20 were symptomatic subjects, and 14 healthy controls. CSF TNF-α, IL-1β, IL-6, IL-8 and YKL-40 were essayed using Meso Scale Discovery antibody-based assays with electrochemiluminiscence detection tetra-plex kit. Chitotriosidase was measured using an in house enzyme activity assay.

Results: CSF TNF-α and IL-1β were below the limit of detection. Mutation carriers had higher YKL-40 (p=0.0028), chitotriasidase (p=0.0145), IL-6 (p=0.0405) and NfL (p=0.0000) than healthy controls. Only NfL (p=0.0062) showed significant differences between presymptomatic and symptomatic subjects. YKL-40 and NfL showed significant association with age, and YKL-40, IL-8, Tau and NfL showed significant association with disease burden score. YKL-40 significantly correlated with disease stage (r=0.33, p=0.046), total functional capacity score (r=-0.46, p=0.015), and UHDRS total motor score (r=0.65, p=0.000), the former and the latter relations remained significant after age-adjustment. IL-6 significantly correlated with disease stage (r=0.33, p=0.043), and Tau significantly correlated with UHDRS total motor score (r=0.44, p=0.007), and both correlation stand still after age-adjustment. NfL significantly correlated with age-adjusted disease stage (r=0.65, p=0.001), age-adjusted total functional capacity (r=-0.38, p=0.008) and age-adjusted and unadjusted total motor score (r=0.47, p=0.000 and r=0.48, p=0.013, respectively). No other significant correlation was observed.

Conclusions: CSF biomarkers of inflammation, microglial activation and neuronal cell death may be useful as biomarkers for HD. YKL-40, IL-6, Tau and NfL can predict clinical phenotype and may be useful as disease activity and pharmacodynamic biomarkers. Further investigation is needed to support our exploratory findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/csf-inflammatory-and-cell-death-biomarkers-in-huntingtons-disease-an-exploratory-cross-sectional-study/