A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington’s disease

Voysey, Z. J., Owen, N. E., Holbrook, J. A., Malpetti, M., Le Draoulec, C., Spindler, L. R. B., Goodman, A. O. G., Lazar, A. S. and Barker, R. A. (2024) A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington’s disease. Journal of Neurology, 271. 7572–7582. ISSN 0340-5354

[thumbnail of Voysey_etal_2024_JNeurol]
Preview
PDF (Voysey_etal_2024_JNeurol) - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

Background: Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington’s disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study. Methods: Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers (n = 21) and controls (n = 14). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington’s Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task and semantic/phonemic fluency tasks. Results: 14/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint (“converters”). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls (p = < 0.001–0.03, η p 2 = 0.25–0.66). The estimated rate of change in NfL was higher in converters than in non-converters (p = 0.03) and controls (p = 0.001). Baseline NfL was able to discriminate converters from non-converters (area under curve = 1.000, p = 0.003). A higher rate of change in NfL was predictive of more severe motor (UHDRS-TMS p = 0.007, β = 0.711, R 2 = 0.468) and cognitive deficits (MoCA p = 0.007, β = − 0.798, R 2 = 0.604; Trail B, p = 0.007, β = 0.772, R 2 = 0.567; phonemic fluency p = 0.035, β = − 0.632, R 2 = 0.345). Conclusions: Our data suggest that (1) NfL longitudinal dynamics in premanifest/transitional HD are non-constant; rising faster in those closer to disease onset, and (2) NfL can identify individuals at risk of conversion to manifest disease and predict clinical trajectory, > 10 years from disease onset.

Item Type: Article
Additional Information: Funding information: ZJ Voysey is funded by an Association of British Neurologists/Guarantors of Brain Clinical Research Fellowship. JA Holbrook was supported by the Centre Parkinson Plus Grant and Cure Parkinson’s Trust. M Malpetti is funded by Race Against Dementia/Alzheimer’s Research UK (no. ARUK-RADF2021A-010, M.M.). LRB Spindler is funded by the UK Medical Research Council. AS Lazar is supported by a Wellcome Trust Seed Award in Science. This research was funded in whole, or in part, by the Wellcome Trust [203151/Z/16/Z, 203151/A/16/Z] and the UKRI Medical Research Council [MC_PC_17230]. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Rights Retention Statement: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled Keywords: biomarker,dementia,huntington’s disease,longitudinal,neurodegeneration,neurofilament light chain,neurology,clinical neurology ,/dk/atira/pure/subjectarea/asjc/2800/2808
Faculty \ School: Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Dementia & Complexity in Later Life
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 01 Nov 2024 10:30
Last Modified: 02 Dec 2024 01:44
URI: https://ueaeprints.uea.ac.uk/id/eprint/97410
DOI: 10.1007/s00415-024-12700-x

Downloads

Downloads per month over past year

Actions (login required)

View Item View Item