D4 Prediction of huntington's disease phenotype by cerebrospinal fluid biomarkers of inflammation and cell death. (13th September 2016)

• Record Type: Journal Article
• Authors: Byrne, Lauren; Rodrigues, Filipe Brogueira; Tabrizi, Sarah J; Zetterberg, Henrik; Wild, Edward J
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 87(2016)Supplement 1
• Page Start: A35
• Page End: A35
• Publication Date: 2016-09-13
• Subjects: biomarkers -- cerebrospinal fluid -- inflammation -- cell death -- pilot projects; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2016-314597.103
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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.