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ToolsVoysey, 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 (12). 7572–7582. ISSN 0340-5354
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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 |
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| 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: | 13 Dec 2024 01:38 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97410 |
| DOI: | 10.1007/s00415-024-12700-x |
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