{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:44:16Z","timestamp":1792046656059,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Huntington's Disease Integrated Staging System (HD\u2010ISS) provides a framework for staging HD but does not incorporate fluid biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to examine neurofilament light chain (NfL) and mutant huntingtin (mHTT) and total tau across HD\u2010ISS stages and their associations with genetic burden, neuroimaging, and clinical measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed cross\u2010sectional analysis of the Barcelona\u2010Huntington's Disease (BCN\u2010HD) cohort with external replication in the multicenter HDClarity study. HD gene expansion carriers were classified as HD\u2010ISS stages 0 to 3. NfL (cerebrospinal fluid [CSF] and plasma), CSF mHTT, total tau, striatal volumes, and Unified Huntington's Disease Rating Scale measures were quantified. Group differences and associations were analyzed using adjusted models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The BCN\u2010HD cohort included 78 participants (50 HD gene expansion carriers [HDGECs], 28 controls) and HDClarity included 218 participants (166 HDGECs, 52 controls). CSF NfL increased across HD\u2010ISS stages and discriminated premanifest from manifest individuals, as well as HD\u2010ISS stage 0 from stage 1. Plasma NfL showed parallel increases and strongly correlated with CSF NfL (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u20090.88,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). More than half of HD\u2010ISS 0 individuals had NfL levels above the age\u2010adjusted 95th percentile (P95) and shorter predicted time to onset (13\u2009years for CSF and 10\u2009years for plasma). From HD\u2010ISS 1 onward, NfL levels exceeded P95 in most individuals. Higher NfL concentrations were associated with genetic burden, striatal atrophy, and clinical measures (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). CSF mHTT was detectable from HD\u2010ISS 0 but showed weaker associations, whereas CSF total tau increased only from HD\u2010ISS 3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      NfL identifies biological activity across the HD\u2010ISS continuum and shows neuroaxonal injury in a subset of individuals classified as stage 0. These findings suggest that fluid biomarkers may complement current HD\u2010ISS criteria and support biological stratification in observational studies and clinical trials. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70550","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:50:48Z","timestamp":1792043448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurofilament Light Chain and Mutant Huntingtin Across Huntington's Disease Integrated Staging System Stages in Huntington Disease: A Cross\u2010Sectional Multimodal Analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9835-0484","authenticated-orcid":false,"given":"Jes\u00fas","family":"P\u00e9rez\u2010P\u00e9rez","sequence":"first","affiliation":[{"name":"Institute of Neuroscience Universitat Aut\u00f2noma de Barcelona  Bellaterra Spain"},{"name":"Movement Disorders Unit Sant Pau Hospital  Barcelona Spain"},{"name":"Department of Medicine Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center for Biomedical Network Research on Neurodegenerative Diseases Instituto de Salud Carlos III  Madrid Spain"},{"name":"Institut de Recerca Sant Pau  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4864-5548","authenticated-orcid":false,"given":"Gonzalo","family":"Olmedo\u2010Saura","sequence":"additional","affiliation":[{"name":"Movement Disorders Unit Sant Pau Hospital  Barcelona Spain"},{"name":"Department of Medicine Universitat Aut\u00f2noma de 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