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Background <p>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.</p> Objective <p>To assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression.</p> Methods <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.</p> Results <p>We consecutively included 44 HD mutation carriers (13 premanifest&#xa0;HD (preHD), 18 in early (early HD)&#xa0;and 13 in advanced (advanced HD)&#xa0;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 &lt; 0.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group&#xa0; (all p values &gt; 0.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values &lt; 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> Conclusions <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.</p>

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Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月1日

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  • Beatrice Heim,
  • Elias Mandler,
  • Marina Peball,
  • Federico Carbone,
  • Katarína Schwarzová,
  • Rina Demjaha,
  • Cansu Tafrali,
  • Arabella Buchmann,
  • Michael Khalil,
  • Atbin Djamshidian,
  • Klaus Seppi

摘要

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.