Dataset Information

Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?

ABSTRACT:

Introduction

Previous studies have suggested cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and total tau are elevated in Huntington's disease (HD) and may be used as markers of disease stage. Biomarkers are needed due to the slow disease progression and the limitations of clinical assessment. This study aims to validate the role of NFL and tau as biomarkers in HD.

Methods

CSF was obtained from a cohort of HD patients and premanifest HD-mutation carriers. Unified Huntington's Disease Rating Scale (UHDRS) testing was performed on all subjects at the time of sampling. NFL and tau concentrations were determined by ELISA. Spearman correlations were calculated with R version 3.2.3.

Results

11 premanifest HD and 12 manifest HD subjects were enrolled. NFL and tau levels were correlated. NFL showed strong correlations with all items included in the clinical assessment (for example the total functional capacity (TFC) (r = - 0.70 p < 0.01) and total motor score (TMS) (r = 0.83p < 0.01). Tau showed slightly weaker correlations (eg. TMS (r = 0.67 p < 0.01); TFC (r = - 0.59 p < 0.01)). NFL was significantly correlated with 5-year probability of disease onset, whereas tau was not.

Conclusion

This study strengthens the case for NFL as a useful biomarker of disease stage. NFL was strongly correlated to all evaluated items in the UHDRS assessment. Tau also has a potential for use as a biomarker but correlations to clinical tests are weaker in this study. We suggest that NFL and possibly tau be used in clinical drug trials as biomarkers of disease progression that are potentially influenced by future disease-modifying therapies.

SUBMITTER: Niemela V

PROVIDER: S-EPMC5328385 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?

Niemelä Valter V Landtblom Anne-Marie AM Blennow Kaj K Sundblom Jimmy J

PloS one 20170227 2

<h4>Introduction</h4>Previous studies have suggested cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and total tau are elevated in Huntington's disease (HD) and may be used as markers of disease stage. Biomarkers are needed due to the slow disease progression and the limitations of clinical assessment. This study aims to validate the role of NFL and tau as biomarkers in HD.<h4>Methods</h4>CSF was obtained from a cohort of HD patients and premanifest HD-mutation carriers. Unified Hu ...[more]

PMID: 28241046

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Project description:BackgroundBlood biomarkers of neuronal damage could facilitate clinical management of and therapeutic development for Huntington's disease. We investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker of neurodegeneration in patients with Huntington's disease.MethodsWe did a retrospective analysis of healthy controls and carriers of CAG expansion mutations in HTT participating in the 3-year international TRACK-HD study. We studied associations between NfL concentrations in plasma and clinical and MRI neuroimaging findings, namely cognitive function, motor function, and brain volume (global and regional). We used random effects models to analyse cross-sectional associations at each study visit and to assess changes from baseline, with and without adjustment for age and CAG repeat count. In an independent London-based cohort of 37 participants (23 HTT mutation carriers and 14 controls), we further assessed whether concentrations of NfL in plasma correlated with those in CSF.FindingsBaseline and follow-up plasma samples were available from 97 controls and 201 individuals carrying HTT mutations. Mean concentrations of NfL in plasma at baseline were significantly higher in HTT mutation carriers than in controls (3·63 [SD 0·54] log pg/mL vs 2·68 [0·52] log pg/mL, p<0·0001) and the difference increased from one disease stage to the next. At any given timepoint, NfL concentrations in plasma correlated with clinical and MRI findings. In longitudinal analyses, baseline NfL concentration in plasma also correlated significantly with subsequent decline in cognition (symbol-digit modality test r=-0·374, p<0·0001; Stroop word reading r=-0·248, p=0·0033), total functional capacity (r=-0·289, p=0·0264), and brain atrophy (caudate r=0·178, p=0·0087; whole-brain r=0·602, p<0·0001; grey matter r=0·518, p<0·0001; white matter r=0·588, p<0·0001; and ventricular expansion r=-0·589, p<0·0001). All changes except Stroop word reading and total functional capacity remained significant after adjustment for age and CAG repeat count. In 104 individuals with premanifest Huntington's disease, NfL concentration in plasma at baseline was associated with subsequent clinical onset during the 3-year follow-up period (hazard ratio 3·29 per log pg/mL, 95% CI 1·48-7·34, p=0·0036). Concentrations of NfL in CSF and plasma were correlated in mutation carriers (r=0·868, p<0·0001).InterpretationNfL in plasma shows promise as a potential prognostic blood biomarker of disease onset and progression in Huntington's disease.FundingMedical Research Council, GlaxoSmithKline, CHDI Foundation, Swedish Research Council, European Research Council, Wallenberg Foundation, and Wolfson Foundation.

Dataset Information

Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?

Introduction

Methods

Results

Conclusion

Publications

Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?

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