{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:39:04Z","timestamp":1780616344802,"version":"3.54.1"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Innsbruck and Medical University of Innsbruck"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Huntington\u2019s disease (HD) is caused by CAG trinucleotide expansion on chromosome 4, leading to mutant Huntingtin production. Premanifest carriers show no obvious clinical signs, and early symptoms progress slowly. Fluid biomarkers like neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), measurable in cerebrospinal fluid and serum (sNfL, sGFAP), offer potential predicting HD progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>To assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>HD mutation carriers were categorized into clinical stages according to their motor symptoms and functional capacities. The Unified HD Rating Scale, cognitive assessments and olfactory tests were used to characterize the patients clinically. Furthermore, sNfL and sGFAP levels were assessed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We consecutively included 44 HD mutation carriers (13 premanifest\u00a0HD (preHD), 18 in early (early HD)\u00a0and 13 in advanced (advanced HD)\u00a0disease stages) and 19 healthy controls (HC). Advanced HD patients performed worse on all clinical tasks and had higher sGFAP and sNfL levels compared to other groups (all p values\u2009&lt;\u20090.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group\u00a0 (all p values\u2009&gt;\u20090.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values\u2009&lt;\u20090.05). ROC curve analysis revealed that the AUC of sGFAP (0.970) exhibited superior discriminatory accuracy compared to sNfL (0.791) levels in separating advanced from early HD patients. By contrast, ROC curve analysis revealed that the AUC of sNFL (0.988) exhibited superior discriminatory accuracy compared to sGFAP (0.609) levels in separating all HD mutation carriers from HC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our study indicates that sNfL can detect changes in very early and premanifest HD stages, whereas sGFAP showed differences in more advanced stages only.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-12901-y","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T14:54:20Z","timestamp":1738421660000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington\u2019s disease"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6749-3044","authenticated-orcid":false,"given":"Beatrice","family":"Heim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Mandler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Peball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Carbone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katar\u00edna","family":"Schwarzov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Demjaha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cansu","family":"Tafrali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arabella","family":"Buchmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atbin","family":"Djamshidian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Seppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"issue":"20","key":"12901_CR1","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1056\/NEJM199405193302001","volume":"330","author":"B Kremer","year":"1994","unstructured":"Kremer B, Goldberg P, Andrew SE et al (1994) A worldwide study of the Huntington\u2019s disease mutation. 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All participants gave written informed consent prior to their participation. The interviews and examinations were carried out in accordance with the principles expressed in the Declaration of Helsinki. On behalf of all co-authors, the first and corresponding author confirm that all authors have read the Journal\u2019s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"174"}}