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Cerebrospinal Fluid Inflammatory Biomarkers Reflect Clinical Severity in Huntington's Disease
Filipe Brogueira Rodrigues1, Lauren M Byrne1, Peter McColgan1
1Huntington's Disease Centre, Institute of Neurology, University College London, London, United Kingdom.
Insights
Huntington
Area of Science:
- Neuroscience
- Immunology
- Biomarker Discovery
Background:
- Immune system activation plays a role in Huntington's disease (HD) pathogenesis.
- Identifying immune biomarkers can aid in disease study and therapeutic response assessment.
- Cerebrospinal fluid (CSF) inflammatory cytokines and microglial markers were investigated in HD patients.
Purpose of the Study:
- To investigate inflammatory cytokines and microglial markers in the CSF of Huntington's disease patients.
- To explore potential CSF biomarkers for Huntington's disease.
Main Methods:
- Assayed CSF levels of TNF-α, IL-1β, IL-6, IL-8, YKL-40, chitotriosidase, total tau, and neurofilament light chain (NFL).
- Compared marker levels between 23 Huntington's disease mutation carriers and 14 healthy controls.
Main Results:
- CSF TNF-α and IL-1β were below the limit of detection.
- Huntington's disease mutation carriers showed significantly higher CSF YKL-40, chitotriosidase, and IL-6 levels compared to controls.
- CSF YKL-40 levels correlated significantly with disease stage, functional capacity, and motor scores.
Conclusions:
- CSF YKL-40 may serve as a potential biomarker for certain aspects of Huntington's disease.
- Further research is required to validate these exploratory findings and establish the role of YKL-40 in HD.
Introduction:
Immune system activation is involved in Huntington's disease (HD) pathogenesis and biomarkers for this process could be relevant to study the disease and characterise the therapeutic response to specific interventions. We aimed to study inflammatory cytokines and microglial markers in the CSF of HD patients.
Methods:
CSF TNF-α, IL-1β, IL-6, IL-8, YKL-40, chitotriosidase, total tau and neurofilament light chain (NFL) from 23 mutation carriers and 14 healthy controls were assayed.
Results:
CSF TNF-α and IL-1β were below the limit of detection. Mutation carriers had higher YKL-40 (p = 0.003), chitotriosidase (p = 0.015) and IL-6 (p = 0.041) than controls. YKL-40 significantly correlated with disease stage (p = 0.007), UHDRS total functional capacity score (r = -0.46, p = 0.016), and UHDRS total motor score (r = 0.59, p = 4.5*10-4) after adjustment for age.
Conclusion:
YKL-40 levels in CSF may, after further study, come to have a role as biomarkers for some aspects of HD. Further investigation is needed to support our exploratory findings.
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