{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:35:00Z","timestamp":1793284500718,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This exploratory pilot study aimed to evaluate serum levels of neurofilament light chain (NfL), peripherin (PRPH), and glial fibrillary acidic protein (GFAP), and to explore their potential associations with nerve conduction studies (NCS) and nerve ultrasound (NUS) in a Swedish cohort of newly diagnosed patients with V50M transthyretin (TTR) amyloidosis (ATTRv).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Seventeen V50M-ATTRv patients exhibiting varying initial clinical symptoms were included for NCS, NUS, and blood analyses of NfL, PRPH, and GFAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      V50M-ATTRv patients had a short disease duration (median, 7\u202fmonths) and predominantly (52.9%) presented with self-reported neuropathic clinical symptoms at disease onset. Sixteen had recently initiated TTR-stabilizing therapy, whereas one remained untreated. Overall, NfL levels were significantly higher in patients than in age-matched controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). This difference remained significant among older individuals (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), but not among younger individuals (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.071). Patients with an earlier age at disease onset had significantly higher PRPH levels compared with those with later disease onset (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.030). Among younger individuals, PRPH levels were higher in patients compared with age-matched controls, but the difference was not significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.200). NCS parameters showed significant associations with both NfL and PRPH, but no such associations were seen with GFAP. None of the neurobiomarkers demonstrated any associations with NUS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this pilot cohort of newly diagnosed Swedish V50M-ATTR patients, NfL was associated with electrophysiological measures of axonal dysfunction, whereas PRPH showed an exploratory signal of interest in younger patients with early disease onset. Larger longitudinal studies are required to determine whether PRPH may serve as a complementary biomarker for the early detection and monitoring of peripheral nerve involvement in ATTRv. Given the pilot design and limited sample size, the subgroup and regression findings should be considered exploratory and hypothesis-generating.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1943011","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:36:45Z","timestamp":1790915805000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early neuro biomarker changes and electrophysiological nerve dysfunction in Swedish V50M hereditary transthyretin amyloidosis: a pilot study"],"prefix":"10.3389","volume":"17","author":[{"given":"Sandra","family":"Arvidsson","sequence":"first","affiliation":[{"name":"Department of Diagnostics and Intervention, Umea University","place":["Ume\u00e5, Sweden"]},{"name":"Department of Public Health and Clinical Medicine, Umea University","place":["Ume\u00e5, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Intissar","family":"Anan","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine, Umea University","place":["Ume\u00e5, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine, Umea University","place":["Ume\u00e5, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Heldestad","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Umea University","place":["Ume\u00e5, Sweden"]},{"name":"Department of Clinical Science, Umea University","place":["Ume\u00e5, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1080\/10408363.2024.2350379","article-title":"Transthyretin mutagenesis: impact on amyloidogenesis and disease","volume":"61","author":"Almeida","year":"2024","journal-title":"Crit Rev Clin Lab Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1186\/s13023-023-02962-5","article-title":"A 15-year consolidated overview of data in over 6000 patients from the transthyretin amyloidosis outcomes survey (THAOS)","volume":"18","author":"Gentile","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3109\/13506129.2013.860027","article-title":"Frequency of the transthyretin Val30Met mutation in the northern Swedish population","volume":"21","author":"Olsson","year":"2014","journal-title":"Amyloid"},{"key":"ref4","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":"ref5","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/path.2411","article-title":"Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis","volume":"216","author":"Ihse","year":"2008","journal-title":"J Pathol"},{"key":"ref6","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":"ref7","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":"ref8","doi-asserted-by":"publisher","first-page":"e01371","DOI":"10.1002\/brb3.1371","article-title":"Advances in the treatment of hereditary transthyretin amyloidosis: a review","volume":"9","author":"Gertz","year":"2019","journal-title":"Brain Behav"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2147\/TCRM.S219979","article-title":"Diagnosis and treatment of hereditary transthyretin amyloidosis (hATTR) polyneuropathy: current perspectives on improving patient care","volume":"16","author":"Luigetti","year":"2020","journal-title":"Ther Clin Risk Manag"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1080\/13506129.2022.2065191","article-title":"Hereditary transthyretin amyloidosis in Sweden: comparisons between a non-endemic and an endemic region","volume":"29","author":"Samuelsson","year":"2022","journal-title":"Amyloid"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320106","article-title":"Neurofilament light chain as a biomarker in neurological disorders","author":"Gaetani","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref12","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":"ref13","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":"ref14","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/jns.12319","article-title":"Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy","volume":"24","author":"van Lieverloo","year":"2019","journal-title":"J Peripher Nerv Syst"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"108624","DOI":"10.1016\/j.intimp.2022.108624","article-title":"Serum glial fibrillary acidic protein is a body fluid biomarker: a valuable prognostic for neurological disease\u2014a systematic review","volume":"107","author":"Heimfarth","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1002\/mus.20983","article-title":"Glial fibrillary acidic protein: a marker of axonal Guillain\u2013Barr\u00e8 syndrome and outcome","volume":"38","author":"Notturno","year":"2008","journal-title":"Muscle Nerve"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"4562","DOI":"10.1093\/brain\/awad234","article-title":"Peripherin is a biomarker of axonal damage in peripheral nervous system disease","volume":"146","author":"Keddie","year":"2023","journal-title":"Brain"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1080\/13506129.2022.2043270","article-title":"Characteristics of patients with autonomic dysfunction in the transthyretin amyloidosis outcomes survey (THAOS)","volume":"29","author":"Barroso","year":"2022","journal-title":"Amyloid"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/mus.20821","article-title":"The molecular biology and clinical features of amyloid neuropathy","volume":"36","author":"Benson","year":"2007","journal-title":"Muscle Nerve"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/mus.20689","article-title":"Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy","volume":"35","author":"Heldestad","year":"2007","journal-title":"Muscle Nerve"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1097\/CND.0000000000000270","article-title":"Hereditary transthyretin amyloidosis: clinical presentation and management updates","volume":"21","author":"Schwartzlow","year":"2020","journal-title":"J Clin Neuromuscul Dis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2239269","DOI":"10.1080\/07853890.2023.2239269","article-title":"Enlarged cross-sectional area in peripheral nerves in Swedish patients with hereditary V30M transthyretin amyloidosis","volume":"55","author":"Arvidsson","year":"2023","journal-title":"Ann Med"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1002\/mus.24168","article-title":"Ultrasound evaluation in transthyretin-related amyloid neuropathy","volume":"50","author":"Granata","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.clinph.2017.01.013","article-title":"Peripheral nerve ultrasonography in patients with transthyretin amyloidosis","volume":"128","author":"Podnar","year":"2017","journal-title":"Clin Neurophysiol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3387","DOI":"10.1007\/s10072-021-05749-3","article-title":"High-resolution ultrasound of peripheral nerves in late-onset hereditary transthyretin amyloidosis with polyneuropathy: similarities and differences with CIDP","volume":"43","author":"Leonardi","year":"2022","journal-title":"Neurol Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1007\/s10072-020-04717-7","article-title":"Nerve ultrasonography findings as possible pitfall in differential diagnosis between hereditary transthyretin amyloidosis with polyneuropathy and chronic inflammatory demyelinating polyneuropathy","volume":"41","author":"Leonardi","year":"2020","journal-title":"Neurol Sci"},{"key":"ref27","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":"ref28","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":"ref29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13506129.2026.2640984","article-title":"Serum peripherin as a disease biomarker in hereditary transthyretin amyloidosis: a multicenter cohort study","author":"Plantone","year":"2026","journal-title":"Amyloid"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation coefficients: appropriate use and interpretation","volume":"126","author":"Schober","year":"2018","journal-title":"Anesth Analg"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3988\/jcn.2022.0340","article-title":"Normative values for serum Neurofilament light chain in US adults","volume":"20","author":"Beltran","year":"2024","journal-title":"J Clin Neurol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1111\/joim.70020","article-title":"Sixty years of experience with hereditary transthyretin amyloidosis: insights from the Swedish transthyretin amyloidosis registry","volume":"298","author":"Stenberg","year":"2025","journal-title":"J Intern Med"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1002\/acn3.51419","article-title":"Evaluation of peripherin in biofluids of patients with motor neuron diseases","volume":"8","author":"Sabbatini","year":"2021","journal-title":"Ann Clin Transl Neurol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e70030","DOI":"10.1111\/ejn.70030","article-title":"Peripherin, a new promising biomarker in neurological disorders","volume":"61","author":"Manco","year":"2025","journal-title":"Eur J Neurosci"},{"key":"ref35","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":"ref36","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":"ref37","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.3390\/diagnostics15202556","article-title":"Peripheral nerve ultrasound findings in hereditary transthyretin amyloidosis in Brazil","volume":"15","author":"Camelo-Filho","year":"2025","journal-title":"Diagnostics (Basel)"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.jns.2009.05.001","article-title":"Familial amyloid polyneuropathy: a clinico-pathologic study","volume":"284","author":"Said","year":"2009","journal-title":"J Neurol Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1002\/alz.12787","article-title":"Confounding factors of Alzheimer\u2019s disease plasma biomarkers and their impact on clinical performance","volume":"19","author":"Pichet Binette","year":"2023","journal-title":"Alzheimers Dement"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1002\/acn3.50972","article-title":"Confounding effect of blood volume and body mass index on blood neurofilament light chain levels","volume":"7","author":"Manouchehrinia","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1002\/acn3.51676","article-title":"Age- and disease-specific reference values for neurofilament light presented in an online interactive support interface","volume":"9","author":"Vermunt","year":"2022","journal-title":"Ann Clin Transl Neurol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"20350","DOI":"10.1038\/s41598-020-76990-7","article-title":"Renal function is associated with blood neurofilament light chain level in older adults","volume":"10","author":"Akamine","year":"2020","journal-title":"Sci Rep"}],"updated-by":[{"DOI":"10.3389\/fneur.2026.2029529","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:00:00Z","timestamp":1793232000000}}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1943011\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:57:52Z","timestamp":1793282272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1943011\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":42,"alternative-id":["10.3389\/fneur.2026.1943011"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1943011","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]},"article-number":"1943011"}}