血清神经丝轻链而非血清胶质纤维酸性蛋白是早期亨廷顿病的一个标志物。
Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington's disease.
作者信息
Heim Beatrice, Mandler Elias, Peball Marina, Carbone Federico, Schwarzová Katarína, Demjaha Rina, Tafrali Cansu, Buchmann Arabella, Khalil Michael, Djamshidian Atbin, Seppi Klaus
机构信息
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Neurology, Medical University of Graz, Graz, Austria.
出版信息
J Neurol. 2025 Feb 1;272(2):174. doi: 10.1007/s00415-025-12901-y.
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.
背景
亨廷顿病（HD）由4号染色体上的CAG三核苷酸扩增引起，导致突变型亨廷顿蛋白产生。症状前携带者无明显临床症状，早期症状进展缓慢。可在脑脊液和血清中检测到的神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）等体液生物标志物为预测HD进展提供了可能。
目的
评估血清GFAP（sGFAP）和血清NfL以及临床生物标志物在不同疾病阶段的作用，并与疾病进展相关联。
方法
根据HD突变携带者的运动症状和功能能力将其分为不同临床阶段。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特征描述。此外，还评估了sNfL和sGFAP水平。
结果
我们连续纳入了44名HD突变携带者（13名症状前HD（preHD）、18名早期HD（early HD）和13名晚期HD（advanced HD）疾病阶段患者）以及19名健康对照（HC）。与其他组相比，晚期HD患者在所有临床任务中的表现更差，sGFAP和sNfL水平更高（所有p值<0.05）。我们未发现preHD组、早期HD组和HC组之间sGFAP水平存在差异（所有p值>0.05）。相比之下，preHD组与早期HD组以及HC组之间的sNfL水平存在显著差异（所有p值<0.05）。受试者工作特征（ROC）曲线分析显示，在区分晚期HD患者与早期HD患者时，sGFAP的曲线下面积（AUC为0.970）比sNfL水平（AUC为0.791）具有更高的鉴别准确性。相比之下，ROC曲线分析显示，在区分所有HD突变携带者与HC时，sNFL的AUC（0.988）比sGFAP水平（AUC为0.609）具有更高的鉴别准确性。
结论
我们的研究表明，sNfL可在HD的极早期和症状前阶段检测到变化，而sGFAP仅在更晚期阶段显示出差异。
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