Related Experiment Video
Updated: Jul 7, 2026
Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
Diagnostic Value of Neurofilament Light Chain and Glial Fibrillary Acidic Protein in Differentiating Primary From
Sara-Jessica Camerin1,2, Cihan Atila1,2, Claudine A Blum1
1Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Background:
Headache is one of the most frequent reasons for emergency department (ED) visits, and distinguishing primary from secondary headache remains challenging. Blood biomarkers may improve early risk stratification. This study evaluates serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) as potential biomarkers in patients presenting with non-traumatic headache to the ED.
Methods:
Secondary analysis of a prospective multicenter case-control study at University Hospital Basel and Aarau, Switzerland. Patients presenting with acute non-traumatic headache were included. Final headache diagnoses were adjudicated by two board-certified neurologists. Blood samples obtained at ED presentation were analyzed for sNfL and sGFAP, excluding patients with conditions known to affect biomarker levels. Primary headache samples were matched to serious secondary headache samples. Biomarker levels were expressed as age-, BMI-, and sex-adjusted Z-scores.
Results:
A total of 82 patients were analyzed (42 serious secondary, 40 primary headache). Median[IQR] sNfL Z-scores were significantly higher in serious secondary compared with primary headache (0.8 [0.0-1.8] vs. 0.2 [-0.3-0.8]; p < 0.01). sGFAP Z-scores showed an even greater difference (1.2 [-0.1-2.3] vs. -0.2 [-0.7-0.2]; p < 0.001). Both biomarkers demonstrated a specificity of 85%, but sGFAP showed higher sensitivity (57% vs. 43%), NPV (65% vs. 59%), and PPV (80% vs. 75%). In multivariable analysis adjusted for clinical risk factors, sGFAP remained independently associated with serious secondary headache (OR 1.9, 95%-CI 1.2-3.4), whereas sNfL did not.
Discussion:
sGFAP may represent a promising biomarker to support differentiation between primary and non-traumatic serious secondary headache in the ED, warranting validation in larger cohorts.
