{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:14:14Z","timestamp":1792818854557,"version":"4.5.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000627","name":"Guarantors of Brain","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000627","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019544","name":"Cambridge Centre for Parkinson-Plus","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015659","name":"Cure Parkinson's Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Race Against Dementia"},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington\u2019s disease (HD). To date, however, there has been no longitudinal study exceeding 3\u00a0years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers (<jats:italic>n<\/jats:italic>\u2009=\u200921) and controls (<jats:italic>n<\/jats:italic>\u2009=\u200914). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington\u2019s Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A\/B task, Symbol Digit Modalities Task and semantic\/phonemic fluency tasks.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>14\/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint (\u201cconverters\u201d). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls (<jats:italic>p<\/jats:italic>\u2009=\u2009&lt;\u20090.001\u20130.03, <jats:italic>\u03b7<\/jats:italic><jats:sub>p<\/jats:sub><jats:sup>2<\/jats:sup>\u2009=\u20090.25\u20130.66). The estimated rate of change in NfL was higher in converters than in non-converters (<jats:italic>p<\/jats:italic>\u2009=\u20090.03) and controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.001). Baseline NfL was able to discriminate converters from non-converters (area under curve\u2009=\u20091.000, <jats:italic>p<\/jats:italic>\u2009=\u20090.003). A higher rate of change in NfL was predictive of more severe motor (UHDRS-TMS <jats:italic>p<\/jats:italic>\u2009=\u20090.007, <jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.711, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.468) and cognitive deficits (MoCA <jats:italic>p<\/jats:italic>\u2009=\u20090.007, <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u2212\u00a00.798, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.604; Trail B, <jats:italic>p<\/jats:italic>\u2009=\u20090.007, <jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.772, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.567; phonemic fluency <jats:italic>p<\/jats:italic>\u2009=\u20090.035, <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u2212\u00a00.632, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.345).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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,\u2009&gt;\u200910\u00a0years from disease onset.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-024-12700-x","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T07:02:05Z","timestamp":1727938925000},"page":"7572-7582","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington\u2019s disease"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4916-6047","authenticated-orcid":false,"given":"Z. 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