Milou Berends, Anne F Brunger, Johan Bijzet, Bart-Jan Kroesen, Gea Drost, Fiete Lange, Charlotte E Teunissen, Sjors In 't Veld, Alexander Fje Vrancken, Reinold O B Gans, Bouke P C Hazenberg, Paul A van der Zwaag, Hans L A Nienhuis
{"title":"将血清神经丝蛋白轻链水平作为遗传性转甲状腺素淀粉样变性病神经元损伤标志物的纵向分析。","authors":"Milou Berends, Anne F Brunger, Johan Bijzet, Bart-Jan Kroesen, Gea Drost, Fiete Lange, Charlotte E Teunissen, Sjors In 't Veld, Alexander Fje Vrancken, Reinold O B Gans, Bouke P C Hazenberg, Paul A van der Zwaag, Hans L A Nienhuis","doi":"10.1080/13506129.2024.2327342","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and <i>TTR</i> variant (<i>TTR</i>v) carriers.</p><p><strong>Methods: </strong>sNfL levels were assessed longitudinally in persistently asymptomatic <i>TTR</i>v carriers (<i>N</i> = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (<i>N</i> = 8), in <i>TTR</i>v carriers who developed polyneuropathy (<i>N</i> = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (<i>N</i> = 20) or TTR-silencer (<i>N</i> = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay.</p><p><strong>Results: </strong>sNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic <i>TTR</i>v carriers. In all <i>TTR</i>v carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment.</p><p><strong>Conclusion: </strong>sNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic <i>TTR</i>v carriers and in monitoring of disease progression and treatment effect.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.\",\"authors\":\"Milou Berends, Anne F Brunger, Johan Bijzet, Bart-Jan Kroesen, Gea Drost, Fiete Lange, Charlotte E Teunissen, Sjors In 't Veld, Alexander Fje Vrancken, Reinold O B Gans, Bouke P C Hazenberg, Paul A van der Zwaag, Hans L A Nienhuis\",\"doi\":\"10.1080/13506129.2024.2327342\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and <i>TTR</i> variant (<i>TTR</i>v) carriers.</p><p><strong>Methods: </strong>sNfL levels were assessed longitudinally in persistently asymptomatic <i>TTR</i>v carriers (<i>N</i> = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (<i>N</i> = 8), in <i>TTR</i>v carriers who developed polyneuropathy (<i>N</i> = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (<i>N</i> = 20) or TTR-silencer (<i>N</i> = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay.</p><p><strong>Results: </strong>sNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic <i>TTR</i>v carriers. In all <i>TTR</i>v carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment.</p><p><strong>Conclusion: </strong>sNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic <i>TTR</i>v carriers and in monitoring of disease progression and treatment effect.</p>\",\"PeriodicalId\":50964,\"journal\":{\"name\":\"Amyloid-Journal of Protein Folding Disorders\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Amyloid-Journal of Protein Folding Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13506129.2024.2327342\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Amyloid-Journal of Protein Folding Disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13506129.2024.2327342","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.
Objective: To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and TTR variant (TTRv) carriers.
Methods: sNfL levels were assessed longitudinally in persistently asymptomatic TTRv carriers (N = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (N = 8), in TTRv carriers who developed polyneuropathy (N = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (N = 20) or TTR-silencer (N = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay.
Results: sNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic TTRv carriers. In all TTRv carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment.
Conclusion: sNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic TTRv carriers and in monitoring of disease progression and treatment effect.
期刊介绍:
Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are:
etiology,
pathogenesis,
histopathology,
chemical structure,
nature of fibrillogenesis;
whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders.
Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.