Beatrice Heim, Elias Mandler, Marina Peball, Federico Carbone, Katarína Schwarzová, Rina Demjaha, Cansu Tafrali, Arabella Buchmann, Michael Khalil, Atbin Djamshidian, Klaus Seppi
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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.</p><p><strong>Objective: </strong>To assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>We consecutively included 44 HD mutation carriers (13 premanifest HD (preHD), 18 in early (early HD) and 13 in advanced (advanced HD) disease 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 < 0.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group (all p values > 0.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values < 0.05). 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.</p><p><strong>Conclusions: </strong>Our study indicates that sNfL can detect changes in very early and premanifest HD stages, whereas sGFAP showed differences in more advanced stages only.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 2","pages":"174"},"PeriodicalIF":5.4000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787204/pdf/","citationCount":"0","resultStr":"{\"title\":\"Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington's disease.\",\"authors\":\"Beatrice Heim, Elias Mandler, Marina Peball, Federico Carbone, Katarína Schwarzová, Rina Demjaha, Cansu Tafrali, Arabella Buchmann, Michael Khalil, Atbin Djamshidian, Klaus Seppi\",\"doi\":\"10.1007/s00415-025-12901-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Huntington's disease (HD) is caused by CAG trinucleotide expansion on chromosome 4, leading to mutant Huntingtin production. 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引用次数: 0
摘要
背景：亨廷顿病（HD）是由4号染色体上CAG三核苷酸扩增引起的，导致亨廷顿蛋白产生突变。先兆携带者无明显临床症状，早期症状进展缓慢。脑脊液和血清中可测量的神经丝光（NfL）和胶质纤维酸性蛋白（GFAP）等液体生物标志物（sNfL, sGFAP）具有预测HD进展的潜力。目的：探讨sGFAP、sNfL及临床生物标志物在不同疾病分期中的作用及其与疾病进展的相关性。方法：将HD突变携带者根据运动症状和功能能力进行临床分期。采用统一HD评定量表、认知评估和嗅觉测试对患者进行临床表征。此外，还评估了sNfL和sGFAP水平。结果：我们连续纳入44例HD突变携带者(13例premanifest HD （preHD)， 18例早期（早期HD）， 13例晚期（晚期HD））和19例健康对照（HC）。与其他组相比，晚期HD患者在所有临床任务中表现较差，sGFAP和sNfL水平较高（均p值0.05）。相比之下，sNfL水平在HD前期、HD早期和HC之间存在显著差异（均p值）。结论：我们的研究表明，sNfL可以检测早期和前期HD阶段的变化，而sGFAP仅在更晚期的HD阶段表现出差异。
Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington's disease.
Background: Huntington's 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.
Objective: To assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression.
Methods: 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.
Results: We consecutively included 44 HD mutation carriers (13 premanifest HD (preHD), 18 in early (early HD) and 13 in advanced (advanced HD) disease 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 < 0.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group (all p values > 0.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values < 0.05). 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.
Conclusions: Our study indicates that sNfL can detect changes in very early and premanifest HD stages, whereas sGFAP showed differences in more advanced stages only.
期刊介绍：
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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