{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:07:07Z","timestamp":1788944827162,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671117"],"award-info":[{"award-number":["81671117"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["81671117"],"award-info":[{"award-number":["81671117"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) usually enters diagnostic pathways after motor symptoms emerge, by which time neural injury has been ongoing. Long-term hereditary ALS cohorts show that some pathogenic-variant carriers may show elevated neurofilament light chain (NfL), mild motor impairment (MMI), electromyographic abnormalities, or imaging changes before clinical manifestation. Since 2022, research has shifted from detecting presymptomatic abnormalities to identifying observable prodromal phenotypes and predicting phenoconversion timing. Operational MMI criteria, longitudinal imaging in chromosome 9 open reading frame 72 (C9orf72) expansion carriers, TAR DNA-binding protein 43 (TDP-43)-related fluid biomarkers, and plasma proteomic models spanning prediction horizons have broadened early identification. The ATLAS study, a trial of tofersen initiated in clinically presymptomatic carriers of superoxide dismutase 1 (SOD1) variants, incorporated specific SOD1 variants and within-person NfL increases into risk monitoring and used these criteria to select participants for the randomized treatment phase. Evidence remains concentrated in a few genetic subtypes, and no single marker accurately predicts individual phenoconversion. Identification requires genotype-specific natural history, serial clinical examinations and biomarker testing, with clinical utility validated in independent longitudinal cohorts and prevention trials.<\/jats:p>","DOI":"10.3390\/diagnostics16172857","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"2857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Presymptomatic Amyotrophic Lateral Sclerosis: From Early Biomarker Detection to Phenoconversion Prediction"],"prefix":"10.3390","volume":"16","author":[{"given":"Min","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing 211112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hexian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing 211112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1596-1042","authenticated-orcid":false,"given":"Qingwen","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing 211112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic lateral sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117054","DOI":"10.1016\/j.jns.2020.117054","article-title":"Time to diagnosis and factors affecting diagnostic delay in amyotrophic lateral sclerosis","volume":"417","author":"Richards","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/ana.25276","article-title":"Neurofilament light: A candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion","volume":"84","author":"Benatar","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3500","DOI":"10.1093\/brain\/awac185","article-title":"Mild motor impairment as prodromal state in amyotrophic lateral sclerosis: A new diagnostic entity","volume":"145","author":"Benatar","year":"2022","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/ana.27116","article-title":"Longitudinal magnetic resonance imaging in asymptomatic C9orf72 mutation carriers distinguishes phenoconverters to amyotrophic lateral sclerosis or amyotrophic lateral sclerosis with frontotemporal dementia","volume":"97","author":"Tan","year":"2025","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1002\/acn3.70187","article-title":"Nerve excitability in asymptomatic carriers and amyotrophic lateral sclerosis patients with C9orf72","volume":"12","author":"Goedee","year":"2025","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105963","DOI":"10.1016\/j.ebiom.2025.105963","article-title":"Patterns of altered in vivo brain metabolism in patients with amyotrophic lateral sclerosis (ALS) and asymptomatic C9orf72 mutation carriers: A cross-sectional 1H and 31P magnetic resonance spectroscopic 7T imaging study","volume":"121","author":"Westeneng","year":"2025","journal-title":"eBioMedicine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ran, X., Wuu, J., Qin, Z.S., McDermott, M.P., Cooper-Knock, J., Li, Y., Granit, V., Grignon, A.L., Lin, E., and Fernandez, M.C. (2026). Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS. Nat. Med.","DOI":"10.1038\/s41591-026-04528-x"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1007\/s13311-022-01237-4","article-title":"Design of a randomized, placebo-controlled, phase 3 trial of tofersen initiated in clinically presymptomatic SOD1 variant carriers: The ATLAS study","volume":"19","author":"Benatar","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of antisense oligonucleotide tofersen for SOD1 ALS","volume":"387","author":"Miller","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1002\/ana.78195","article-title":"High prevalence of SOD1 pathogenic variants in the UK Biobank: Implications for early intervention in amyotrophic lateral sclerosis","volume":"99","author":"Gagliardi","year":"2026","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1080\/21678421.2019.1646769","article-title":"Neurofilaments in pre-symptomatic ALS and the impact of genotype","volume":"20","author":"Benatar","year":"2019","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1093\/brain\/awaf269","article-title":"Neurodegenerative disease in C9orf72 repeat expansion carriers: Population risk and effect of UNC13A","volume":"148","author":"Gao","year":"2025","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e410","DOI":"10.1212\/NXG.0000000000000410","article-title":"Differential subcellular expression of P525L FUS as a putative biomarker for ALS phenoconversion","volume":"6","author":"Caputo","year":"2020","journal-title":"Neurol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ruffo, P., Catalano, S., La Bella, V., and Conforti, F.L. (2023). Deregulation of plasma microRNA expression in a TARDBP-ALS family. Biomolecules, 13.","DOI":"10.3390\/biom13040706"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1474-4422(21)00414-2","article-title":"Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1466","DOI":"10.1212\/WNL.0000000000012632","article-title":"Prediagnostic neurofilament light chain levels in amyotrophic lateral sclerosis","volume":"97","author":"Bjornevik","year":"2021","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1080\/21678421.2023.2285428","article-title":"Plasma neurofilament light levels show elevation two years prior to diagnosis of amyotrophic lateral sclerosis in the UK Biobank","volume":"25","author":"Smith","year":"2024","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1080\/21678421.2025.2539898","article-title":"Identifying diagnostic markers in the health records of prediagnostic amyotrophic lateral sclerosis patients","volume":"27","author":"Simoni","year":"2026","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1080\/21678421.2025.2574687","article-title":"Prodromal symptoms in amyotrophic lateral sclerosis from the perspective of the patient and of the caregiver","volume":"27","author":"Kraneburg","year":"2026","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104521","DOI":"10.1016\/j.ebiom.2023.104521","article-title":"Metabolic alterations precede neurofilament changes in presymptomatic ALS gene carriers","volume":"90","author":"Dorst","year":"2023","journal-title":"eBioMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41591-023-02788-5","article-title":"A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD","volume":"30","author":"Irwin","year":"2024","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e213917","DOI":"10.1212\/WNL.0000000000213917","article-title":"Proposed research criteria for mild motor impairment as a prodromal syndrome in amyotrophic lateral sclerosis","volume":"105","author":"Benatar","year":"2025","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1093\/brain\/awn071","article-title":"Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis","volume":"131","author":"Vucic","year":"2008","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1136\/jnnp.73.2.199","article-title":"Detection of preclinical motor neurone loss in SOD1 mutation carriers using motor unit number estimation","volume":"73","author":"Aggarwal","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/ana.27133","article-title":"Elevated cerebrospinal fluid ubiquitin carboxyl-terminal hydrolase isozyme L1 in asymptomatic C9orf72 hexanucleotide repeat expansion carriers","volume":"97","author":"Dellar","year":"2025","journal-title":"Ann. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaai7866","DOI":"10.1126\/scitranslmed.aai7866","article-title":"Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis","volume":"9","author":"Gendron","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"859","DOI":"10.15252\/emmm.201607486","article-title":"Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS\/FTD","volume":"9","author":"Lehmer","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1001\/jamaneurol.2015.1872","article-title":"Cortical function in asymptomatic carriers and patients with C9orf72 amyotrophic lateral sclerosis","volume":"72","author":"Geevasinga","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1136\/jnnp-2020-324647","article-title":"Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis","volume":"92","author":"Kmetzsch","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e70989","DOI":"10.1002\/alz.70989","article-title":"Detection of TDP-43 seeds in CSF of presymptomatic and symptomatic genetic FTD\/ALS","volume":"21","author":"Dellarole","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e16379","DOI":"10.1111\/ene.16379","article-title":"Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study","volume":"31","author":"Meyer","year":"2024","journal-title":"Eur. J. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/nan.12511","article-title":"Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with amyotrophic lateral sclerosis","volume":"45","author":"Gille","year":"2019","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/ana.24954","article-title":"Serum neurofilament light: A biomarker of neuronal damage in multiple sclerosis","volume":"81","author":"Disanto","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/S1474-4422(19)30354-0","article-title":"Serum neurofilament light chain in genetic frontotemporal dementia: A longitudinal, multicenter cohort study","volume":"18","author":"Meeter","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e1338","DOI":"10.1212\/WNL.0000000000006282","article-title":"Serum neurofilament light: A biomarker of neuroaxonal injury after ischemic stroke","volume":"91","author":"Tiedt","year":"2018","journal-title":"Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"R\u00fcbsamen, N., Willemse, E.A.J., Leppert, D., Wiendl, H., Nauck, M., Karch, A., Kuhle, J., and Berger, K. (2022). A method to combine neurofilament light measurements from blood serum and plasma in clinical and population-based studies. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.894119"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/ana.27054","article-title":"Population-based evidence for the use of serum neurofilaments as individual diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis","volume":"96","author":"Witzel","year":"2024","journal-title":"Ann. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Vacchiano, V., Mastrangelo, A., Zenesini, C., Masullo, M., Quadalti, C., Avoni, P., Polischi, B., Cherici, A., Capellari, S., and Salvi, F. (2021). Plasma and CSF neurofilament light chain in amyotrophic lateral sclerosis: A cross-sectional and longitudinal study. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.753242"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107415","DOI":"10.1016\/j.nbd.2026.107415","article-title":"Plasma NfL, GFAP and pTau181 define distinct biological axes in amyotrophic lateral sclerosis","volume":"224","author":"Senerchia","year":"2026","journal-title":"Neurobiol. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhang, L., Ji, T., Wu, C., Zhang, S., Tang, L., Zhang, N., Liu, X., and Fan, D. (2022). Serum neurofilament light chain levels may be a marker of lower motor neuron damage in amyotrophic lateral sclerosis. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.833507"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Verde, F., Milone, I., Colombo, E., Maranzano, A., Solca, F., Torre, S., Doretti, A., Gentile, F., Manini, A., and Bonetti, R. (2023). Phenotypic correlates of serum neurofilament light chain levels in amyotrophic lateral sclerosis. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1132808"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Shahim, P., Norato, G., Sinaii, N., Zetterberg, H., Blennow, K., Chan, L., and Grunseich, C. (2024). Neurofilaments in sporadic and familial amyotrophic lateral sclerosis: A systematic review and meta-analysis. Genes, 15.","DOI":"10.3390\/genes15040496"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dziadkowiak, E., Marschollek, K., Kwa\u015bniak-Nowakowska, A., Zimny, A., Ra\u0142owska-Gmoch, W., Boro\u0144, M., and Koszewicz, M. (2026). Establishing diagnostic and differential diagnostic criteria for amyotrophic lateral sclerosis. J. Clin. Med., 15.","DOI":"10.3390\/jcm15010287"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e70902","DOI":"10.1002\/alz.70902","article-title":"Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease","volume":"21","author":"Saracino","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e71669","DOI":"10.1002\/alz.71669","article-title":"Changes in body composition in genetic C9orf72 carriers: The role of the hypothalamus and thalamus","volume":"22","author":"Ahmed","year":"2026","journal-title":"Alzheimers Dement."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/acn3.51039","article-title":"Cortical hyperexcitability evolves with disease progression in ALS","volume":"7","author":"Menon","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/ana.27305","article-title":"Cortical excitability as a prognostic and phenotypic stratification biomarker in amyotrophic lateral sclerosis","volume":"98","author":"Ranieri","year":"2025","journal-title":"Ann. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Nogueira-Machado, J.A., da Silva Albanaz, A.T., and Rocha-Silva, F. (2025). MicroRNA as a potential biomarker for amyotrophic lateral sclerosis (ALS). Sclerosis, 3.","DOI":"10.3390\/sclerosis3020016"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Swash, M., and de Carvalho, M. (2025). Dynamics of onset and progression in amyotrophic lateral sclerosis. Brain Sci., 15.","DOI":"10.3390\/brainsci15060601"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1136\/jnnp-2024-334339","article-title":"Guidance for clinical management of pathogenic variant carriers at elevated genetic risk for ALS\/FTD","volume":"96","author":"Benatar","year":"2025","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1890","DOI":"10.1002\/jgc4.1890","article-title":"Individuals\u2019 experiences in genetic counseling and predictive testing for familial amyotrophic lateral sclerosis","volume":"34","author":"Steigerwald","year":"2025","journal-title":"J. Genet. Couns."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/WAD.0000000000000458","article-title":"Patient and relative experiences and decision-making about genetic testing and counseling for familial ALS and FTD: A systematic scoping review","volume":"35","author":"Crook","year":"2021","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1002\/acn3.51895","article-title":"ALS Genetic Testing and Counseling Guidelines Expert Panel. Evidence-based consensus guidelines for ALS genetic testing and counseling","volume":"10","author":"Roggenbuck","year":"2023","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41431-024-01718-4","article-title":"Genetic testing for monogenic forms of motor neuron disease\/amyotrophic lateral sclerosis in unaffected family members","volume":"33","author":"Howard","year":"2025","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s41436-021-01171-4","article-title":"Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: A policy statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"23","author":"Miller","year":"2021","journal-title":"Genet. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101454","DOI":"10.1016\/j.gim.2025.101454","article-title":"ACMG SF v3.3 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"27","author":"Lee","year":"2025","journal-title":"Genet. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1001\/jamaneurol.2025.4946","article-title":"Long-term tofersen in SOD1 amyotrophic lateral sclerosis","volume":"83","author":"Miller","year":"2026","journal-title":"JAMA Neurol."},{"key":"ref_59","unstructured":"ClinicalTrials.gov (2026, July 15). A Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults with a Confirmed Superoxide Dismutase 1 Mutation (NCT04856982), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04856982."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1093\/brain\/awaf290","article-title":"Design considerations for C9orf72 disease prevention trials","volume":"148","author":"Benatar","year":"2025","journal-title":"Brain"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S1474-4422(24)00216-3","article-title":"Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: A phase 1, randomised, double-blind, placebo-controlled, multiple ascending dose study","volume":"23","author":"Rothstein","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.1007\/s00415-024-12513-y","article-title":"Clinical and genetic characteristics of 1672 cases of amyotrophic lateral sclerosis in China: A single-center retrospective study","volume":"271","author":"Shen","year":"2024","journal-title":"J. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Pasqualucci, E., Angeletti, D., Rosso, P., Fico, E., Zoccali, F., Tirassa, P., De Virgilio, A., de Vincentiis, M., and Severini, C. (2025). Management of dysarthria in amyotrophic lateral sclerosis. Cells, 14.","DOI":"10.3390\/cells14141048"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2857\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:21:01Z","timestamp":1788942061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":63,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diagnostics16172857"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16172857","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]}}}