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This study examined cerebrospinal fluid biomarkers in 88 people with Huntington's disease to understand striatal brain volume loss. Researchers found that while higher neurofilament light levels correlated with smaller putamen volume (indicating neurodegeneration), higher myeloperoxidase levels were associated with larger putamen volume even after accounting for neurofilament light and genetic disease burden. The addition of myeloperoxidase measurements improved the ability to explain variation in striatal volume loss beyond existing markers.
Why it matters
These findings suggest that immune-related proteins like myeloperoxidase may provide complementary information about Huntington's disease progression that is not captured by standard neuroaxonal injury markers alone. This could potentially lead to more comprehensive biomarker panels for tracking disease progression and monitoring treatment responses in Huntington's disease.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background: The primary neuroanatomical site of Huntington-s disease (HD) pathology resides in the striatum and its atrophy identifies important disease progression from HD-ISS Stage 0 to Stage 1. Immune-associated proteins may capture variation in HD that is incompletely represented by markers of neuroaxonal injury. Objectives: To determine whether cerebrospinal-fluid myeloperoxidase contributes information about striatal volume loss beyond genetic disease burden and neurofilament light. Methods: Cross-sectional data from 88 persons with HD were analyzed. Cerebrospinal-fluid myeloperoxidase and neurofilament light were measured with a nucleic acid-linked immunosandwich assay. Normalized putamen volume was derived from structural magnetic resonance imaging. Linear regression adjusted for genetic disease burden and sex. Results: Higher neurofilament light was associated with smaller normalized putamen volume (standardized {beta} = -0.322, (P=.0066)). Higher myeloperoxidase was associated with larger normalized putamen volume after adjustment for genetic disease burden, sex, and neurofilament light (standardized {beta} = 0.183, (P=.0386)). Adding myeloperoxidase increased explained variance in striatal loss. Conclusions: Cerebrospinal fluid myeloperoxidase contributed modest incremental information about striatal volume in this cross-sectional sample. Independent longitudinal studies are needed to determine its biological source, temporal behavior, and potential biomarker value. Findings advance efforts to characterize multicomponent biological markers of HD.