Neurology · 1 h ago
Neurofilament Light Levels Track Huntington Disease Stages, Including Early Neuroaxonal Injury
A cross-sectional analysis of 78 participants, with external replication in 218 participants, examined fluid biomarkers across Huntington disease stages. Neurofilament light chain increased across stages and was elevated in more than half of stage 0 gene expansion carriers, suggesting it may complement existing staging criteria.
- NfL increased across Huntington disease stages in two cohorts.
- More than half of stage 0 individuals had elevated NfL.
- Plasma and CSF NfL correlated strongly.
- Cross-sectional findings do not establish longitudinal predictive performance.
The Huntington’s Disease Integrated Staging System (HD-ISS) does not currently incorporate fluid biomarkers. Researchers examined neurofilament light chain (NfL), mutant huntingtin (mHTT), and total tau in a cross-sectional analysis of the Barcelona-Huntington’s Disease cohort, with external replication in HDClarity. The cohorts included 78 participants (50 gene expansion carriers and 28 controls) and 218 participants (166 carriers and 52 controls), respectively. Adjusted analyses assessed biomarker differences across stages 0–3 and associations with genetic burden, striatal volumes, and clinical measures.
Cerebrospinal fluid (CSF) NfL increased across stages, distinguishing premanifest from manifest disease and stage 0 from stage 1. Plasma NfL showed parallel increases and correlated strongly with CSF NfL (ρ = 0.88; P < 0.001). More than half of stage 0 individuals exceeded the age-adjusted 95th percentile for NfL, with shorter predicted times to onset reported as 13 years for CSF and 10 years for plasma. Most individuals exceeded this threshold from stage 1 onward. Higher NfL was associated with genetic burden, striatal atrophy, and clinical measures (all P < 0.001).
CSF mHTT was detectable at stage 0 but showed weaker associations; total tau increased only from stage 3. These findings support investigating NfL as a complement to HD-ISS for biological stratification. However, the cross-sectional design cannot establish longitudinal predictive performance, and predicted onset times are not observed outcomes. Full text was unavailable for assessment.
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Movement Disorders: Neurofilament Light Chain and Mutant Huntingtin Across Huntington's Disease Integrated Staging System Stages in Huntington Disease: A Cross‐Sectional Multimodal Analysis ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.