Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Thomas Meyer - , Berlin Institute of Health at Charité, Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany. (Author)
  • Marie Dreger - , Berlin Institute of Health at Charité (Author)
  • Torsten Grehl - , Alfried Krupp Krankenhaus (Author)
  • Ute Weyen - , BG University Hospital Bergmannsheil Bochum (Author)
  • Dagmar Kettemann - , Berlin Institute of Health at Charité (Author)
  • Patrick Weydt - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • René Günther - , Department of Neurology, German Center for Neurodegenerative Diseases, Dresden site (Partner: DZNE of the Helmholtz Association), University Hospital Carl Gustav Carus Dresden (Author)
  • Paul Lingor - , German Center for Neurodegenerative Diseases (DZNE) (Author)
  • Susanne Petri - , Hannover Medical School (MHH) (Author)
  • Jan Christoph Koch - , University Medical Center Göttingen (Author)
  • Julian Großkreutz - , Universitätsklinikum Schleswig-Holstein - Campus Lübeck (Author)
  • Annekathrin Rödiger - , Jena University Hospital (Author)
  • Petra Baum - , University Hospital Leipzig (Author)
  • Andreas Hermann - , German Center for Neurodegenerative Diseases (DZNE) (Author)
  • Johannes Prudlo - , German Center for Neurodegenerative Diseases (DZNE) (Author)
  • Matthias Boentert - , University Hospital Münster (Author)
  • Jochen H Weishaupt - , Universitätsmedizin Mannheim (Author)
  • Wolfgang N Löscher - , Innsbruck Medical University (Author)
  • Johannes Dorst - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Ulm (Author)
  • Yasemin Koc - , Berlin Institute of Health at Charité (Author)
  • Sarah Bernsen - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Isabell Cordts - , Klinikum Rechts der Isar (MRI TUM) (Author)
  • Maximilian Vidovic - , Department of Neurology, University Hospital Carl Gustav Carus Dresden (Author)
  • Robert Steinbach - , Jena University Hospital (Author)
  • Moritz Metelmann - , University Hospital Leipzig (Author)
  • Vera E Kleinveld - , Innsbruck Medical University (Author)
  • Jenny Norden - , Berlin Institute of Health at Charité (Author)
  • Albert Ludolph - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Ulm (Author)
  • Bertram Walter - , Berlin Institute of Health at Charité (Author)
  • Peggy Schumann - , Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany. (Author)
  • Christoph Münch - , Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany. (Author)
  • Péter Körtvélyessy - , Berlin Institute of Health at Charité (Author)
  • André Maier - , Berlin Institute of Health at Charité (Author)

Abstract

OBJECTIVE: To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS).

METHODS: In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail-arm, flail-leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival.

RESULTS: Mean sNfL was - compared to typMN (75.7 pg/mL, n = 1791) - significantly lower in LMNp (45.1 pg/mL, n = 413), UMNp (58.7 pg/mL n = 206), and PLS (37.6 pg/mL, n = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL, n = 669), limb (64.1 pg/mL, n = 1305), flail-arm (46.4 pg/mL, n = 283), flail-leg (53.6 pg/mL, n = 141), and thoracic (74.5 pg/mL, n = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months, n = 2862) showed minor monthly changes (<0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed (p < 0.001).

CONCLUSIONS: This study underscored the correlation of ALS phenotypes - differentiated for motor neuron involvement and region of onset/propagation - with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice.

Details

Original languageEnglish
Article numbere16379
JournalEuropean journal of neurology
Volume31
Issue number9
Publication statusPublished - Sept 2024
Peer-reviewedYes

External IDs

PubMedCentral PMC11295170
Scopus 85195572111

Keywords

Keywords

  • Humans, Amyotrophic Lateral Sclerosis/blood, Neurofilament Proteins/blood, Male, Female, Middle Aged, Phenotype, Aged, Longitudinal Studies, Disease Progression, Biomarkers/blood, Adult, Germany/epidemiology