Journal of neurology · 2025
Serum GFAP predicts survival in advanced ALS: a prospective multicenter study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Jung Hee-Jae, Jeong Woo-Seung, Kang Heung-Won, Kang Minsung, Lee Eun-Jae, Lim Young-Min, Park Jin-Sung, Kim Hyunjin
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
WHAT IS ALREADY KNOWN ON THIS TOPIC: 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.
WHAT THIS STUDY ADDS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
WHAT IS ALREADY KNOWN ON THIS TOPIC: 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.
WHAT THIS STUDY ADDS: 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.