Journal Article

DZNE-2025-01367

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Motor phenotypes and neurofilament light chain in genetic amyotrophic lateral sclerosis-results from a multicenter screening program.

Schmitt, P. ; Schumann, P. ; Koerbs, A. ; Lin, H.-J. ; Grehl, T. ; Weyen, U. ; Petri, S. ; Rödiger, A. ; Steinbach, R. ; Großkreutz, J. ; Bernsen, S.DZNE* ; Weydt, P.DZNE* ; Wolf, J. ; Günther, R.DZNE* ; Baum, P. ; Metelmann, M. ; Weishaupt, J. H. ; Streubel, B. ; Kasper, D. C. ; Koc, Y. ; Kettemann, D. ; Norden, J. ; Walter, B. ; Münch, C. ; Spittel, S. ; Maier, A. ; Körtvelyessy, P.Extern* ; Meyer, T.

2025
Steinkopff [Darmstadt]

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Please use a persistent id in citations: doi:10.1007/s00415-025-13555-6

Abstract: In genetic amyotrophic lateral sclerosis (ALS), the clinical phenotypes, disease progression and neurofilament light chain (NfL) levels are incompletely characterized.In a total cohort of 1988 ALS patients, a subcohort of genetic ALS linked to C9orf72 (n = 137), SOD1 (n = 54), TARDBP (n = 27), and FUS (n = 19) was investigated. The phenotypes of onset region, propagation and motor neuron involvement were analyzed according to the OPM classification. Serum NfL (sNfL) was measured and related to ALS progression (ALSPR, monthly change of ALS Functional Rating Scale-Revised). To quantify NfL elevation relative to ALSPR, the logNfL(index), the log-transformed ratio of sNfL to ALSPR was calculated.C9orf72-associated ALS showed frequent bulbar onset (n = 42.6%), higher ALSPR (0.95, SD 0.84), highest NfL (116.3, SD 72.7 pg/mL) and logNfL(index) (5.02, SD 0.88). SOD1-ALS had mostly limb onset (n = 96.1%), slower ALSPR (0.57, SD 0.60), high NfL (76.1, SD 61.4 pg/mL) and a comparably high logNfL(index) (4.94, SD 1.03). FUS-ALS exhibited mostly limb onset (82.4%), lower motor neuron dysfunction (70.6%), a wide range of faster (22.2%) to slower ALSPR (55.6%), lower NfL (66.2, SD 32.9) and logNfL(4.65, SD 0.9). TARDBP-ALS displayed the lowest ALSPR (0.53, SD 0.52), the lowest NfL (43.3, SD 31.8 pg/mL) and the lowest logNfL(index) (4.40, SD 0.7).In C9orf72-ALS, the phenotype and NfL profile are close to typical ALS. The finding of distinct phenotypes and NfL patterns in SOD1-, FUS- and TARDBP-associated ALS underscores the relevance of genetic ALS for prognostic counseling, clinical trial design, treatment expectations and unraveling of pathogenic mechanisms in ALS.

Keyword(s): Humans (MeSH) ; Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Amyotrophic Lateral Sclerosis: blood (MeSH) ; Amyotrophic Lateral Sclerosis: physiopathology (MeSH) ; Amyotrophic Lateral Sclerosis: diagnosis (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; C9orf72 Protein: genetics (MeSH) ; Phenotype (MeSH) ; Aged (MeSH) ; RNA-Binding Protein FUS: genetics (MeSH) ; Superoxide Dismutase-1: genetics (MeSH) ; Adult (MeSH) ; Disease Progression (MeSH) ; Cohort Studies (MeSH) ; DNA-Binding Proteins: genetics (MeSH) ; ALS progression ; Genetic ALS ; Neurofilament ; Phenotype ; Neurofilament Proteins ; neurofilament protein L ; C9orf72 Protein ; C9orf72 protein, human ; RNA-Binding Protein FUS ; Superoxide Dismutase-1 ; TARDBP protein, human ; FUS protein, human ; SOD1 protein, human ; DNA-Binding Proteins

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Contributing Institute(s):

1. Clinical Neuroimaging (AG Radbruch)
2. Clinical Research Coordination (Clinical Research (Bonn))
3. Translational Parkinson Research (AG Falkenburger)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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