Cerebrospinal Fluid Inflammatory Biomarkers Reflect Clinical Severity in Huntington’s Disease

<div><p>Introduction</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p></div

Relationship between CSF concentration of YKL-40 and measures of disease progression and clinical severity.

<p>a, disease stage; b, UHDRS total functional score; c, UHDRS total motor score. The p-values for partial Pearson’s correlation coefficient adjusted for age are shown.</p

Comparison in CSF levels of inflammatory molecules between 14 healthy controls versus 23 gene expansion carriers.

<p>The p-values for unpaired two-tailed t-test (Il-8) or Wilcoxon log-rank test (YKL-40, chitotriosidase, IL-6) are shown.</p

Characteristics of included participants by disease stage.

<p>Characteristics of included participants by disease stage.</p