ArticleEBioMedicine2024
Mapping neurodegeneration across the Huntington's disease spectrum: a five-year longitudinal analysis of plasma neurofilament light.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review with Meta-Analysis of Biofluid Markers for Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Pooled it
- Fluid and Imaging Biomarkers in Huntington's Disease.Current neurology and neuroscience reports · 2026Review
- Effects of time-restricted eating in early-stage Huntington's disease: a pilot study.Nature metabolism · 2026Article
- Meal timing as medicine: clinical evidence for intermittent fasting in Huntington's disease.Nature metabolism · 2026Article
- Spontaneous speech and language measures as predictive biomarkers of clinically meaningful disease progression and neurodegeneration in Huntington's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- A machine learning-derived speech index as a biomarker for Huntington's disease severity.Journal of neurology · 2026Article
- Discovery and Targeted Proteomic Studies Reveal Striatal Markers Validated for Huntington's Disease.Annals of clinical and translational neurology · 2026Article
- Neural and biomarker correlates of the Parkinson's Disease-Cognitive Rating Scale in Huntington's disease.Neuroimage. Reports · 2026Article
- Longitudinal evaluation of serum neurofilament light levels in normal healthy volunteers: defining a threshold of concern.Journal of neurology · 2025Article
- Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington's disease.Journal of neurology · 2025Article
- A Pilot Proteomic Analysis of Huntington's Disease by Functional Capacity.Brain sciences · 2025Article
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Authors and funding
3 authors.
Funding
Abstract
backgroundNeurofilament light (NfL) has previously been highlighted as a potential biomarker for Huntington's Disease (HD) using cross-sectional analyses. Our study aim was to investigate how longitudinal trajectories of plasma NfL relate to HD disease stage.
methods108 participants [78 individuals with the HD mutation, and 30 healthy controls (HC)] were included in this study. Individuals with the HD mutation were categorised separately by both HD-Integrated Staging System (HD-ISS) (Study 1) and PIN score-Approximated Staging System (PASS) (Study 2) criteria. Plasma NfL trajectories were examined using Mixed Linear Modeling (MLM); associations with symptom presentation were assessed using Spearman's rho correlations.
findingsThe MLM coefficients for disease stage (HD-ISS β = 32.73, p < 0.0001; PASS β = 33.00, p < 0.0001) and disease stage∗time (HD-ISS β = 7.85, p = 0.004; PASS β = 6.58, p = 0.0047) suggest these are significant contributors to plasma NfL levels. In addition, the plasma NfL rate of change varied significantly across time (HD-ISS β = 3.14, p = 0.04; PASS β = 2.94, p = 0.050). The annualised rate of change was 8.32% for HC; 10.55%, 12.75% and 15.62% for HD-ISS Stage ≤1, Stage 2, and Stage 3, respectively; and 12.13%, 10.46%, 10.33%, 17.52%, for PASS Stage 0, Stage 1, Stage 2, and Stage 3, respectively. Plasma NfL levels correlated with the Symbol Digit Modalities Test (SDMT) in HD-ISS Stage ≤1, and both SDMT and Total Motor Score in Stage 3 (ps < 0.01).
interpretationOur findings suggest that plasma NfL levels increase linearly across earlier disease stages, correlating with the cognitive SDMT measure. Thereafter, an increase or surge in plasma NfL levels, paired with correlations with both cognitive and motor measures, suggest a late acceleration in clinical and pathological progression.
fundingNIH (NS111655); the UCSD HDSA CoE; the UCSD ADRC (NIH-NIA P30 AG062429).
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