282906 20260112103811.0 10.1007/s00415-025-13555-6 doi pmid:41388206 pmid pmc:PMC12700978 pmc 0367-004X ISSN 0012-1037 ISSN 0340-5354 ISSN 1432-1459 ISSN DZNE-2025-01367 English 610 Schmitt, Philipp 0009-0008-1643-0079 0 Motor phenotypes and neurofilament light chain in genetic amyotrophic lateral sclerosis-results from a multicenter screening program. [Darmstadt] 2026 Steinkopff article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1768206258_9861 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de ALS progression Other Genetic ALS Other Neurofilament Other Phenotype Other Neurofilament Proteins NLM Chemicals neurofilament protein L NLM Chemicals C9orf72 Protein NLM Chemicals C9orf72 protein, human NLM Chemicals RNA-Binding Protein FUS NLM Chemicals Superoxide Dismutase-1 EC 1.15.1.1 NLM Chemicals TARDBP protein, human NLM Chemicals FUS protein, human NLM Chemicals SOD1 protein, human NLM Chemicals DNA-Binding Proteins NLM Chemicals 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 Schumann, Peggy 1 Koerbs, Alexander 2 Lin, Hsuen-Ju 3 Grehl, Torsten 4 Weyen, Ute 5 Petri, Susanne 6 Rödiger, Annekathrin 7 Steinbach, Robert 8 Großkreutz, Julian 9 Bernsen, Sarah P:(DE-2719)9000485 10 dzne Weydt, Patrick P:(DE-2719)9001116 11 dzne Wolf, Joachim 12 Günther, René P:(DE-2719)2811849 13 dzne Baum, Petra 14 Metelmann, Moritz 15 Weishaupt, Jochen H 16 Streubel, Berthold 17 Kasper, David C 18 Koc, Yasemin 19 Kettemann, Dagmar 20 Norden, Jenny 21 Walter, Bertram 22 Münch, Christoph 23 Spittel, Susanne 24 Maier, André 25 Körtvelyessy, Peter P:(DE-2719)2812030 26 dzne Meyer, Thomas 27 10.1007/s00415-025-13555-6 Vol. 273, no. 1, p. 22 PERI:(DE-600)1421299-7 1 22 Journal of neurology 273 2026 0367-004X http://pub.dzne.de/record/282906/files/DZNE-2025-01367.pdf OpenAccess http://pub.dzne.de/record/282906/files/DZNE-2025-01367.pdf?subformat=pdfa pdfa OpenAccess oai:pub.dzne.de:282906 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)9000485 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)9001116 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 13 P:(DE-2719)2811849 External Institute I:(DE-HGF)0 Extern 26 P:(DE-2719)2812030 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 2025 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-10 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-10 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2024-12-10 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2024-12-10 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2024-12-10 OpenAccess StatID:(DE-HGF)0510 StatID JCR StatID:(DE-HGF)0100 StatID J NEUROL : 2022 2024-12-10 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2024-12-10 DEAL Springer StatID:(DE-HGF)3002 StatID 2024-12-10 ger DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-10 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-10 Peer Review StatID:(DE-HGF)0030 StatID ASC 2024-12-10 IF >= 5 StatID:(DE-HGF)9905 StatID J NEUROL : 2022 2024-12-10 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-10 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC Nationallizenz StatID:(DE-HGF)0420 StatID 2024-12-10 ger DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-10 I:(DE-2719)5000075 AG Radbruch Clinical Neuroimaging 0 I:(DE-2719)1011001 Clinical Research (Bonn) Clinical Research Coordination 1 I:(DE-2719)1710012 AG Falkenburger Translational Parkinson Research 2 journal VDB I:(DE-2719)5000075 I:(DE-2719)1011001 I:(DE-2719)1710012 UNRESTRICTED FullTexts