{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:55:24Z","timestamp":1792166124684,"version":"4.4.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Neurofilament light chain levels (NfL) have emerged as a biomarker for early diagnosis and follow-up of hereditary transthyretin variant amyloidosis (ATTRv). We evaluated the most accurate technique for NfL quantifying in ATTRv healthy carriers and symptomatic patients in real-life practice, and assessed whether NfL may represent a reliable biomarker of disease onset and progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum NfL were measured using ELISA and the single-molecule array (SIMoA) technique. Disease severity was assessed with a polyneuropathy disability score (PND).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy-five subjects with pathogenic transthyretin variant (40 ATTRv healthy carriers and 35 ATTRv patients) were enrolled. We observed a significant correlation between ELISA and SIMoA assay (Pearson\u2019s R2-value\u202f=\u202f0.9899). Compared to healthy carriers, patients with symptomatic ATTRv had statistically higher serum NfL levels (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). We propose a NfL cut-off of 7.9\u202fpg.\/mL to distinguish between healthy carriers and ATTRv patients with high diagnostic accuracy (AUC\u202f=\u202f0.847; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001; sensitivity\u202f=\u202f90.0%; specificity\u202f=\u202f55.0%), whereas the NfL threshold of 18.4\u202fpg.\/mL discriminated the transition from patients with PND I to PND\u202f\u2265\u202fII (AUC\u202f=\u202f0.695; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001; sensitivity\u202f=\u202f67.0%, specificity\u202f=\u202f86%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serum NfL can be accurately quantified using both ELISA and SIMoA array, and it seems to be a reliable biomarker to detect the transition from presymptomatic to symptomatic disease onset and to monitor disease progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1660344","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:18:25Z","timestamp":1759897105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical utility of neurofilament light chain as a biomarker for disease onset and progression in hereditary transthyretin amyloidosis"],"prefix":"10.3389","volume":"16","author":[{"given":"\u00c1lvaro","family":"Gragera-Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Borrachero Garro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Mu\u00f1oz Beamud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Manovel S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Gonz\u00e1lez Mac\u00edas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Pizarro S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Jim\u00e9nez Heffernan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Serrano Mira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Mac\u00edas Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Garcia Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1097\/WCO.0000000000000289","article-title":"First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy","volume":"29","author":"Adams","year":"2016","journal-title":"Curr Opin Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1080\/13506129.2024.2327342","article-title":"Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis","volume":"31","author":"Berends","year":"2024","journal-title":"Amyloid"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1136\/jnnp-2011-301299","article-title":"Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas","volume":"83","author":"Koike","year":"2012","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1080\/13506129.2019.1708716","article-title":"Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy","volume":"27","author":"Maia","year":"2020","journal-title":"Amyloid"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13023-017-0726-x","article-title":"Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters and treatment algorithm","volume":"13","author":"Sekijima","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1007\/s40120-021-00267-y","article-title":"A descriptive analysis of ATTR amyloidosis in Spain from the transthyretin amyloidosis outcomes survey","volume":"10","author":"Gonz\u00e1lez-Moreno","year":"2021","journal-title":"Neurol Ther"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/B978-0-444-52902-2.00038-2","article-title":"Transthyretin familial amyloid polyneuropathy","volume":"115","author":"Plant\u00e9-Bordeneuve","year":"2013","journal-title":"Handb Clin Neurol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/S1474-4422(23)00334-4","article-title":"Hereditary transthyretin amyloid neuropathies: advances in pathophysiology, biomarkers, and treatment","volume":"22","author":"Adams","year":"2023","journal-title":"Lancet Neurol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e16070","DOI":"10.1111\/ene.16070","article-title":"Serum neurofilament light chain: a promising early diagnostic biomarker for hereditary transthyretin amyloidosis?","volume":"31","author":"Romano","year":"2024","journal-title":"Eur J Neurol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1242815","DOI":"10.3389\/fneur.2023.1242815","article-title":"Hereditary transthyretin amyloidosis: a comprehensive review with a focus on peripheral neuropathy","volume":"14","author":"Poli","year":"2023","journal-title":"Front Neurol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/s41598-023-50212-2","article-title":"Biomarkers of axonal damage to favor early diagnosis in variant transthyretin amyloidosis (A-ATTRv)","volume":"14","author":"Gonz\u00e1lez-Moreno","year":"2024","journal-title":"Sci Rep"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.rdc.2013.02.012","article-title":"Amyloidosis: a clinical overview","volume":"39","author":"Hazenberg","year":"2013","journal-title":"Rheum Dis Clin N Am"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"6416","DOI":"10.1007\/s00415-022-11276-8","article-title":"Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update","volume":"269","author":"Brannagan","year":"2022","journal-title":"J Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa1716153","article-title":"Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis","volume":"379","author":"Adams","year":"2018","journal-title":"N Engl J Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1007\/s00415-019-09671-9","article-title":"Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosis","volume":"267","author":"Coelho","year":"2020","journal-title":"J Neurol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1097\/WCO.0000000000000290","article-title":"Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis","volume":"29","author":"Obici","year":"2016","journal-title":"Curr Opin Neurol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s10072-020-04889-2","article-title":"Hereditary transthyretin amyloidosis overview","volume":"43","author":"Manganelli","year":"2022","journal-title":"Neurol Sci"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/ejhf.2113","article-title":"Use of biomarkers to diagnose and manage cardiac amyloidosis","volume":"23","author":"Castiglione","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41582-024-00955-x","article-title":"Neurofilaments as biomarkers in neurological disorders - towards clinical application","volume":"20","author":"Khalil","year":"2024","journal-title":"Nat Rev Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e412","DOI":"10.1212\/WNL.0000000000011090","article-title":"Neurofilament light chain as a biomarker of hereditary transthyretin-mediated amyloidosis","volume":"96","author":"Ticau","year":"2021","journal-title":"Neurology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13506129.2023.2232520","article-title":"Treatment response and neurofilament light chain levels with long-term patisiran in hereditary transthyretin-mediated amyloidosis with polyneuropathy: 24-month results of an open-label extension study","volume":"31","author":"Ticau","year":"2024","journal-title":"Amyloid"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1111\/jns.12524","article-title":"Serum neurofilament light chain as a reliable biomarker of hereditary transthyretin-related amyloidosis-a Swiss reference center experience","volume":"28","author":"Loser","year":"2023","journal-title":"J Peripher Nerv Syst"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"3770","DOI":"10.3390\/ijms25073770","article-title":"Neurofilament light chains in systemic amyloidosis: a systematic review","volume":"25","author":"Berends","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1111\/jns.12350","article-title":"Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis","volume":"24","author":"Kapoor","year":"2019","journal-title":"J Peripher Nerv Syst"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3208","DOI":"10.1007\/s11064-024-04244-3","article-title":"Emerging trends: Neurofilament biomarkers in precision neurology","volume":"49","author":"Sharma","year":"2024","journal-title":"Neurochem Res"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1136\/jnnp-2021-327909","article-title":"Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis","volume":"93","author":"Carroll","year":"2022","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1007\/s00415-019-09688-0","article-title":"Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy","volume":"268","author":"Adams","year":"2021","journal-title":"J Neurol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1080\/13506129.2019.1627312","article-title":"Assessment of patients with hereditary transthyretin amyloidosis - understanding the impact of management and disease progression","volume":"26","author":"Concei\u00e7\u00e3o","year":"2019","journal-title":"Amyloid"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1016\/j.medcli.2024.02.013","article-title":"Early diagnosis in ATTRv amyloidosis, how early is enough? How early is possible?","volume":"162","author":"Concei\u00e7\u00e3o","year":"2024","journal-title":"Med Clin (Barc)"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1750-1172-8-31","article-title":"Guideline of transthyretin-related hereditary amyloidosis for clinicians","volume":"8","author":"Ando","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"ref31","year":"2023"},{"key":"ref32","year":"2025"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1515\/cclm-2022-0007","article-title":"Pre-analytical stability of serum biomarkers for neurological disease: neurofilament-light, glial fibrillary acidic protein and contactin-1","volume":"60","author":"van Lierop","year":"2022","journal-title":"Clin Chem Lab Med"},{"key":"ref34","year":"2024"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1515\/cclm-2022-1181","article-title":"Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood","volume":"61","author":"Andreasson","year":"2023","journal-title":"Clin Chem Lab Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"935382","DOI":"10.3389\/fneur.2022.935382","article-title":"Development of a highly sensitive Neurofilament light chain assay on an automated immunoassay platform","volume":"13","author":"Lee","year":"2022","journal-title":"Front Neurol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.4155\/bio-2019-0163","article-title":"Establishment of neurofilament light chain Simoa assay in cerebrospinal fluid and blood","volume":"11","author":"Hendricks","year":"2019","journal-title":"Bioanalysis"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"10787","DOI":"10.3390\/ijms241310787","article-title":"A comparison of two analytical approaches for the quantification of Neurofilament light chain, a biomarker of axonal damage in multiple sclerosis","volume":"24","author":"Pafiti","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1515\/cclm-2015-1195","article-title":"Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and simoa","volume":"54","author":"Kuhle","year":"2016","journal-title":"Clin Chem Lab Med"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"104177","DOI":"10.1016\/j.msard.2022.104177","article-title":"Serum neurofilament levels in patients with multiple sclerosis: a comparison of SIMOA and high sensitivity ELISA assays and contributing factors to ELISA levels","volume":"67","author":"Revendova","year":"2022","journal-title":"Mult Scler Relat Disord"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1080\/13506129.2023.2187678","article-title":"Neurofilament light chain as a biomarker for monitoring response to change in treatment in hereditary ATTR amyloidosis","volume":"30","author":"Sato","year":"2023","journal-title":"Amyloid"},{"key":"ref42","author":"Gragera-Mart\u00ednez","year":""},{"key":"ref43","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S1474-4422(22)00009-6","article-title":"Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study","volume":"21","author":"Benkert","year":"2022","journal-title":"Lancet Neurol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1660344\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:18:26Z","timestamp":1759897106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1660344\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":43,"alternative-id":["10.3389\/fneur.2025.1660344"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1660344","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]},"article-number":"1660344"}}