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Background <p>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.</p> Methods <p>Serum NfL, GFAP, and BDNF levels were measured using ultrasensitive single-molecule array (SIMOA) assays in two independent ALS cohorts from Asan Medical Center (<i>n</i> = 65) and Kyungpook National University Chilgok Hospital (<i>n</i> = 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.</p> Results <p>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, <i>p</i> = 0.011; GFAP: τ = 0.160, <i>p</i> = 0.023), though only NfL correlated with disease progression rate (<i>r</i> = 0.309, <i>p</i> = 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, <i>p</i> = 0.002).</p> Conclusions <p>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.</p>

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Serum GFAP predicts survival in advanced ALS: a prospective multicenter study

  • 期刊论文

  • 发表日期：

    2025年7月24日

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  • Hee-Jae Jung,
  • Woo-Seung Jeong,
  • Heung-Won Kang,
  • Minsung Kang,
  • Eun-Jae Lee,
  • Young-Min Lim,
  • Jin-Sung Park,
  • Hyunjin Kim

摘要

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.