Comparative Performances of 4 Serum NfL Assays, pTau181, and GFAP in Patients With Amyotrophic Lateral Sclerosis
Mondesert, E. (Univ Montpellier)
Delaby, Constance (Institut de Recerca Sant Pau)
De La Cruz, E. (Univ Montpellier)
Kuhle, Jens (University of Basel)
Benkert, P. (University of Basel)
Pradeilles, N. (Univ Montpellier)
Duchiron, M. (Univ Montpellier)
Morchikh, M. (Univ Montpellier)
Camu, W. (Univ Montpellier)
Cristol, J.P. (Univ Montpellier)
Hirtz, C. (Univ Montpellier)
Esselin, F. (Univ Montpellier)
Lehmann, Sylvain (Univ Montpellier)
Universitat Autònoma de Barcelona

Date:	2025
Abstract:	Background and Objectives Selecting the most appropriate blood tests is crucial for the management of patients with amyotrophic lateral sclerosis (ALS). This study evaluates the diagnostic and prognostic performance of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (pTau181) biomarkers in ALS to establish their clinical relevance and cutoff values. Methods In a cohort of patients from the ALS center in Montpellier, we conducted a head-to-head comparison of 4 different technologies and 3 distinct serum analytes: NfL was tested using the ultrasensitive Simoa and the microfluidic Ella platforms, along with 2 assays recently set up on clinical-grade platforms: Lumipulse and Elecsys. We also used Elecsys to assess serum GFAP and pTau181. Results Our cohort included 139 patients with ALS and 70 non-ALS patients, with a mean age of 66. 1 ± 11. 4 years and 47. 4% of women. The mean follow-up was 42 ± 26. 3 months for patients with ALS and 141. 6 ± 106. 3 months for non-ALS patients, with a mortality rate of 85. 5% vs 7. 7%. There was a high correlation between all methods tested for serum NfL quantification (R = 0. 939 to 0. 963). The area under the curve (AUC) for ALS diagnosis was 0. 889 (0. 827-0. 932) for NfL Simoa, 0. 906 (0. 847-0. 944) for Ella, 0. 912 (0. 853-0. 948) for Lumipulse, and 0. 910 (0. 851-0. 946) for Elecsys. Serum pTau181 and GFAP showed poor diagnostic performance with AUCs of 0. 565 (0. 472-0. 649) and 0. 546 (0. 461-0. 636), respectively. Kaplan-Meier survival analysis revealed significant hazard ratios (4. 4-5. 4) for blood NfL. Patients with ALS had a 40%-50% chance of surviving 50 weeks below the prognostic cutoff values while survival rates dropped to near zero above. NfL and GFAP levels were associated with age and body mass index, considered confounding factors. pTau181 levels varied significantly in patients with ALS depending on the site of onset. Discussion This study demonstrates the consistent performance of 4 immunoassays for serum NfL quantification in ALS. NfL showed high diagnostic and prognostic accuracy, making it suitable for individual assessment, unlike GFAP or pTau181. We propose diagnostic and prognostic cutoff values for serum NfL, providing a basis for wider implementation, especially with the clinically accredited Lumipulse and Elecsys platforms, which are becoming standard practice.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aged ; Amyotrophic Lateral Sclerosis ; Biomarkers ; Cohort Studies ; Female ; Glial Fibrillary Acidic Protein ; Humans ; Male ; Middle Aged ; Neurofilament Proteins ; Phosphorylation ; Prognosis ; Tau Proteins
Published in:	Neurology, Vol. 104 Núm. 6 (26 2025) , p. e213400, ISSN 1526-632X

DOI: 10.1212/WNL.0000000000213400
PMID: 40009787

10 p, 844.6 KB

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