Jung Hee-Jae, Jeong Woo-Seung, Kang Heung-Won, Kang Minsung, Lee Eun-Jae, Lim Young-Min, Park Jin-Sung, Kim Hyunjin
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
University of Ulsan College of Medicine, Seoul, Republic of Korea.
J Neurol. 2025 Jul 24;272(8):532. doi: 10.1007/s00415-025-13272-0.
Neurofilament light chain (NfL) is a well-established biomarker of axonal damage in amyotrophic lateral sclerosis (ALS), but its limited disease specificity warrants the identification of complementary markers. This study aimed to evaluate the prognostic value of serum glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) as adjunctive biomarkers to NfL in ALS.
Serum NfL, GFAP, and BDNF levels were measured using ultrasensitive single-molecule array (SIMOA) assays in two independent ALS cohorts from Asan Medical Center (n = 65) and Kyungpook National University Chilgok Hospital (n = 53), along with 15 healthy controls. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Associations with clinical severity, disease progression rate, and survival were evaluated using correlation analyses, Kaplan-Meier survival estimates, and Cox proportional hazards models.
Serum NfL, GFAP, and BDNF levels were significantly elevated in ALS versus controls, with area under the curve (AUC) values of 0.969, 0.613, and 0.875, for NfL, GFAP, and BDNF, respectively. NfL and GFAP levels increased with advancing King's stage (NfL: τ = 0.226, p = 0.011; GFAP: τ = 0.160, p = 0.023), though only NfL correlated with disease progression rate (r = 0.309, p = 0.001). Notably, elevated GFAP was independently associated with poorer survival in advanced ALS (King's stage 3-4), with a hazard ratio of 6.907 (95% CI: 1.978-24.119, p = 0.002).
While NfL remains a robust marker of ALS progression, GFAP may serve as an independent prognostic marker in late-stage disease. Combining these markers may enhance prognostic accuracy and support personalized ALS care.
Neurofilament light chain (NfL) is a widely accepted biomarker for axonal damage in ALS and correlates with disease progression. However, its lack of disease specificity limits its standalone prognostic value, necessitating the discovery of complementary biomarkers to improve prognostic accuracy.
This study demonstrates that while NfL remains a strong indicator of ALS progression, glial fibrillary acidic protein (GFAP) serves as an independent prognostic marker, particularly in advanced stages of the disease. Furthermore, it shows that serum BDNF levels are also elevated in ALS patients.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: Combining NfL and GFAP as a biomarker panel could significantly enhance prognostic accuracy and facilitate more personalized treatment strategies for ALS patients, especially in later disease stages. This could guide clinical trial design and improve patient stratification for therapeutic interventions.
神经丝轻链（NfL）是肌萎缩侧索硬化症（ALS）中轴突损伤公认的生物标志物，但其疾病特异性有限，因此需要识别互补标志物。本研究旨在评估血清胶质纤维酸性蛋白（GFAP）和脑源性神经营养因子（BDNF）作为ALS中NfL辅助生物标志物的预后价值。
在来自峨山医学中心（n = 65）和庆北国立大学칠곡医院（n = 53）的两个独立ALS队列以及15名健康对照中，使用超灵敏单分子阵列（SIMOA）检测法测量血清NfL、GFAP和BDNF水平。使用受试者工作特征（ROC）曲线分析评估诊断性能。使用相关性分析、Kaplan-Meier生存估计和Cox比例风险模型评估与临床严重程度、疾病进展率和生存率的关联。
与对照组相比，ALS患者血清NfL、GFAP和BDNF水平显著升高，NfL、GFAP和BDNF的曲线下面积（AUC）值分别为0.969、0.613和0.875。NfL和GFAP水平随King分期进展而升高（NfL：τ = 0.226，p = 0.011；GFAP：τ = 0.160，p = 0.023），但只有NfL与疾病进展率相关（r = 0.309，p = 0.001）。值得注意的是，GFAP升高与晚期ALS（King分期3-4）患者较差的生存率独立相关，风险比为6.907（95% CI：1.978-24.119，p = 0.002）。
虽然NfL仍然是ALS进展的可靠标志物，但GFAP可能是晚期疾病的独立预后标志物。联合使用这些标志物可能提高预后准确性，并支持个性化的ALS护理。
神经丝轻链（NfL）是ALS中轴突损伤广泛接受的生物标志物，与疾病进展相关。然而，其缺乏疾病特异性限制了其独立的预后价值，因此需要发现互补生物标志物以提高预后准确性。
本研究表明，虽然NfL仍然是ALS进展的有力指标，但胶质纤维酸性蛋白（GFAP）是独立的预后标志物，特别是在疾病晚期。此外，研究表明ALS患者血清BDNF水平也升高。
本研究可能对研究、实践或政策产生的影响：将NfL和GFAP作为生物标志物组合可显著提高预后准确性，并为ALS患者，特别是疾病后期患者制定更个性化的治疗策略。这可为临床试验设计提供指导，并改善治疗干预的患者分层。
