Amyloid-Journal of Protein Folding Disorders最新文献

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ATTR- and AFib amyloid - two different types of amyloid in the annular ligament of trigger finger. ATTR和AFib淀粉样蛋白是扳机指环状韧带中两种不同类型的淀粉样蛋白。
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-06-23 DOI: 10.1080/13506129.2023.2226298
Christian Treitz, Neelis Müller-Marienburg, Rolf Rüdiger Meliß, Peter Urban, Hans-Detlef Axmann, Frank Siebert, Karsten Becker, Klaus Martens, Hans-Michael Behrens, Eva Gericke, Andreas Tholey, Christoph Röcken
{"title":"ATTR- and AFib amyloid - two different types of amyloid in the annular ligament of trigger finger.","authors":"Christian Treitz, Neelis Müller-Marienburg, Rolf Rüdiger Meliß, Peter Urban, Hans-Detlef Axmann, Frank Siebert, Karsten Becker, Klaus Martens, Hans-Michael Behrens, Eva Gericke, Andreas Tholey, Christoph Röcken","doi":"10.1080/13506129.2023.2226298","DOIUrl":"10.1080/13506129.2023.2226298","url":null,"abstract":"<p><strong>Introduction: </strong>Histological examination of tissue specimens obtained during surgical treatment of trigger finger frequently encountered unclassifiable amyloid deposits in the annular ligament. We systematically explored this unknown type by a comprehensive analysis using histology, immunohistochemistry, and quantitative mass spectrometry-based proteomics.</p><p><strong>Methods: </strong>205 tissue specimens of annular ligaments were obtained from 172 patients. Each specimen was studied by histology and immunohistochemistry. Tissue specimens obtained from ten patients with histology proven amyloid in annular ligament were analysed by label-free quantitative proteomics. Histological and immunohistochemical findings were correlated with patient demographics.</p><p><strong>Results: </strong>Amyloid was present as band like deposits along the surface of annular ligament, dot like or patchy deposits within the matrix. Immunohistochemistry identified ATTR amyloid in 92 specimens (mostly patchy in the matrix), while the band like deposits of 100 specimens remained unclassifiable. Proteomic profiles identified the unknown amyloid as most likely of fibrinogen origin. The complete cohort was re-examined by immunohistochemistry using a custom-made antibody and confirmed the presence of fibrinogen alpha-chain (FGA) in a hitherto unclassifiable type of amyloid in annular ligament.</p><p><strong>Conclusion: </strong>Our study shows that two different types of amyloid affect the annular ligament, ATTR amyloid and AFib amyloid, with distinct demographic patient characteristics and histomorphological deposition patterns.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"394-406"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis. 腰椎管狭窄症患者黄韧带淀粉样蛋白的患病率。
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-07-11 DOI: 10.1080/13506129.2023.2230516
Francesco Marchi, Chiara Kessler, Daniela Distefano, Lodovico Terzi di Bergamo, Luca Fumagalli, Manuela Averaimo, Emanuele Crupi, Fabio Bergamini, Giorgia Melli, Georg Stussi, Davide Rossi, Claudio Gobbi, Paolo Ripellino, Emanuele Pravatà, Dominique E Kuhlen, Christoph Röcken, Pietro Scarone, Bernhard Gerber, Adalgisa Condoluci
{"title":"Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis.","authors":"Francesco Marchi, Chiara Kessler, Daniela Distefano, Lodovico Terzi di Bergamo, Luca Fumagalli, Manuela Averaimo, Emanuele Crupi, Fabio Bergamini, Giorgia Melli, Georg Stussi, Davide Rossi, Claudio Gobbi, Paolo Ripellino, Emanuele Pravatà, Dominique E Kuhlen, Christoph Röcken, Pietro Scarone, Bernhard Gerber, Adalgisa Condoluci","doi":"10.1080/13506129.2023.2230516","DOIUrl":"10.1080/13506129.2023.2230516","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS.</p><p><strong>Methods: </strong>Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC).</p><p><strong>Results: </strong>Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (<i>p</i> < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, <i>p</i> = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed.</p><p><strong>Conclusions: </strong>Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"416-423"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rare-variant collapsing and bioinformatic analyses for amyloidosis, dementia and Parkinson's disease in the UK biobank reveal novel susceptibility loci. 英国生物库中淀粉样变性、痴呆和帕金森病的罕见变异崩溃和生物信息学分析揭示了新的易感位点。
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-07-14 DOI: 10.1080/13506129.2023.2226299
Bengt Zöller, Eric Manderstedt, Christina Lind-Halldén, Christer Halldén
{"title":"Rare-variant collapsing and bioinformatic analyses for amyloidosis, dementia and Parkinson's disease in the UK biobank reveal novel susceptibility loci.","authors":"Bengt Zöller, Eric Manderstedt, Christina Lind-Halldén, Christer Halldén","doi":"10.1080/13506129.2023.2226299","DOIUrl":"10.1080/13506129.2023.2226299","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"442-444"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9781141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A rare occurrence and near miss! Should a TTR gene test be routinely performed for suspected ATTR-cardiomyopathy? 难得的机会,差一点就错过了!对疑似atr型心肌病患者是否应常规进行TTR基因检测?
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-07-11 DOI: 10.1080/13506129.2023.2232516
Bharadwaj Satyavolu, Genise Green, Anthony Jake Demetris, Prem Soman
{"title":"A rare occurrence and near miss! Should a TTR gene test be routinely performed for suspected ATTR-cardiomyopathy?","authors":"Bharadwaj Satyavolu, Genise Green, Anthony Jake Demetris, Prem Soman","doi":"10.1080/13506129.2023.2232516","DOIUrl":"10.1080/13506129.2023.2232516","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"449-450"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9757535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patients with transthyretin amyloidosis enrolled in THAOS between 2018 and 2021 continue to experience substantial diagnostic delay. 2018年至2021年期间纳入THAOS的甲状腺转视蛋白淀粉样变患者继续经历严重的诊断延迟。
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-07-17 DOI: 10.1080/13506129.2023.2229484
Teresa Coelho, Angela Dispenzieri, Martha Grogan, Isabel Conceição, Márcia Waddington-Cruz, Arnt V Kristen, Jonas Wixner, Igor Diemberger, Juan Gonzalez-Moreno, Mathew S Maurer, Violaine Planté-Bordeneuve, Pablo Garcia-Pavia, Ivailo Tournev, Jose Gonzalez-Costello, Eve Cariou, Alejandra González-Duarte, Oliver Glass, Doug Chapman, Leslie Amass
{"title":"Patients with transthyretin amyloidosis enrolled in THAOS between 2018 and 2021 continue to experience substantial diagnostic delay.","authors":"Teresa Coelho, Angela Dispenzieri, Martha Grogan, Isabel Conceição, Márcia Waddington-Cruz, Arnt V Kristen, Jonas Wixner, Igor Diemberger, Juan Gonzalez-Moreno, Mathew S Maurer, Violaine Planté-Bordeneuve, Pablo Garcia-Pavia, Ivailo Tournev, Jose Gonzalez-Costello, Eve Cariou, Alejandra González-Duarte, Oliver Glass, Doug Chapman, Leslie Amass","doi":"10.1080/13506129.2023.2229484","DOIUrl":"10.1080/13506129.2023.2229484","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"445-448"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping cellular response to destabilized transthyretin reveals cell- and amyloidogenic protein-specific signatures. 绘制细胞对不稳定甲状腺素的反应揭示了细胞和淀粉样蛋白特异性特征。
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-07-13 DOI: 10.1080/13506129.2023.2224494
Sabrina Ghosh, Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Devin Kenney, Carly S Golden, Camille V Edwards, Vaishali Sanchorawala, Lawreen H Connors, Richard M Giadone, George J Murphy
{"title":"Mapping cellular response to destabilized transthyretin reveals cell- and amyloidogenic protein-specific signatures.","authors":"Sabrina Ghosh, Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Devin Kenney, Carly S Golden, Camille V Edwards, Vaishali Sanchorawala, Lawreen H Connors, Richard M Giadone, George J Murphy","doi":"10.1080/13506129.2023.2224494","DOIUrl":"10.1080/13506129.2023.2224494","url":null,"abstract":"<p><strong>Background: </strong>In ATTR amyloidosis, transthyretin (TTR) protein is secreted from the liver and deposited as toxic aggregates at downstream target tissues. Despite recent advancements in treatments for ATTR amyloidosis, the mechanisms underlying misfolded TTR-mediated cellular damage remain elusive.</p><p><strong>Methods: </strong>In an effort to define early events of TTR-associated stress, we exposed neuronal (SH-SY5Y) and cardiac (AC16) cells to wild-type and destabilized TTR variants (TTR<sup>V122I</sup> (p.V142I) and TTR<sup>L55P</sup> (p.L70P)) and performed transcriptional (RNAseq) and epigenetic (ATACseq) profiling. We subsequently compared TTR-responsive signatures to cells exposed to destabilized antibody light chain protein associated with AL amyloidosis as well as ER stressors (thapsigargin, heat shock).</p><p><strong>Results: </strong>In doing so, we observed overlapping, yet distinct cell type- and amyloidogenic protein-specific signatures, suggesting unique responses to each amyloidogenic variant. Moreover, we identified chromatin level changes in AC16 cells exposed to mutant TTR that resolved upon pre-incubation with kinetic stabilizer tafamidis.</p><p><strong>Conclusions: </strong>Collectively, these data provide insight into the mechanisms underlying destabilized protein-mediated cellular damage and provide a robust resource representing cellular responses to aggregation-prone proteins and ER stress.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"379-393"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9985612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of complementarity-determining regions 1 and 3 in pathologic amyloid formation by human immunoglobulin κ1 light chains. 互补决定区1和3在人免疫球蛋白κ1轻链病理淀粉样蛋白形成中的作用。
IF 5.2 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-05-22 DOI: 10.1080/13506129.2023.2212397
Elena S Klimtchuk, Daniele Peterle, Esther Bullitt, Lawreen H Connors, John R Engen, Olga Gursky
{"title":"Role of complementarity-determining regions 1 and 3 in pathologic amyloid formation by human immunoglobulin κ1 light chains.","authors":"Elena S Klimtchuk, Daniele Peterle, Esther Bullitt, Lawreen H Connors, John R Engen, Olga Gursky","doi":"10.1080/13506129.2023.2212397","DOIUrl":"10.1080/13506129.2023.2212397","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin light chain (LC) amyloidosis is a life-threatening disease complicated by vast numbers of patient-specific mutations. We explored 14 patient-derived and engineered proteins related to κ1-family germline genes IGKVLD-33*01 and IGKVLD-39*01.</p><p><strong>Methods: </strong>Hydrogen-deuterium exchange mass spectrometry analysis of conformational dynamics in recombinant LCs and their fragments was integrated with studies of thermal stability, proteolytic susceptibility, amyloid formation and amyloidogenic sequence propensity. The results were mapped on the structures of native and fibrillary proteins.</p><p><strong>Results: </strong>Proteins from two κ1 subfamilies showed unexpected differences. Compared to their germline counterparts, amyloid LC related to IGKVLD-33*01 was less stable and formed amyloid faster, whereas amyloid LC related to IGKVLD-39*01 had similar stability and formed amyloid slower, suggesting different major factors influencing amyloidogenesis. In 33*01-related amyloid LC, these factors involved destabilization of the native structure and probable stabilization of amyloid. The atypical behavior of 39*01-related amyloid LC stemmed from increased dynamics/exposure of amyloidogenic segments in βC'V and βEV that could initiate aggregation and decreased dynamics/exposure near the Cys23-Cys88 disulfide.</p><p><strong>Conclusions: </strong>The results suggest distinct amyloidogenic pathways for closely related LCs and point to the complementarity-defining regions CDR1 and CDR3, linked via the conserved internal disulfide, as key factors in amyloid formation.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"364-378"},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9552302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuropathy progression in hereditary transthyretin amyloidosis (ATTRv) patients after liver transplantation. 遗传性甲状腺转蛋白淀粉样变(ATTRv)患者肝移植后神经病变的进展。
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-12-01 Epub Date: 2023-06-23 DOI: 10.1080/13506129.2023.2226295
Catarina Falcão de Campos, Isabel Conceição
{"title":"Neuropathy progression in hereditary transthyretin amyloidosis (ATTRv) patients after liver transplantation.","authors":"Catarina Falcão de Campos, Isabel Conceição","doi":"10.1080/13506129.2023.2226295","DOIUrl":"10.1080/13506129.2023.2226295","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"440-441"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9670809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tafamidis concentration required for transthyretin stabilisation in cerebrospinal fluid. 脑脊液中转甲状腺素稳定所需的Tafamidis浓度。
IF 5.2 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-09-01 Epub Date: 2023-01-24 DOI: 10.1080/13506129.2023.2167595
Felix J Tsai, Marcus Jaeger, Teresa Coelho, Evan T Powers, Jeffery W Kelly
{"title":"Tafamidis concentration required for transthyretin stabilisation in cerebrospinal fluid.","authors":"Felix J Tsai, Marcus Jaeger, Teresa Coelho, Evan T Powers, Jeffery W Kelly","doi":"10.1080/13506129.2023.2167595","DOIUrl":"10.1080/13506129.2023.2167595","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin (TTR) amyloidosis (ATTRv) initially presents as a polyneuropathy and/or a cardiomyopathy. Central nervous system (CNS) pathology in ATTRv amyloidosis, including focal neurological episodes, dementia, cerebrovascular bleeding, and seizures, appears around a decade later. Wild-type (WT) TTR amyloidosis (ATTRwt) causes a cardiomyopathy. CNS pathology risk likely also increases in these patients as cardiomyopathy progresses. Herein, we study tafamidis-mediated TTR kinetic stabilisation in cerebrospinal fluid (CSF).</p><p><strong>Methods: </strong>Varying tafamidis concentrations (50-1000 nM) were added to CSF from healthy donors or ATTRv patients, and TTR stabilisation was measured <i>via</i> the decrease in dissociation rate.</p><p><strong>Results: </strong>Tafamidis meglumine (Vyndaqel) can be dosed at 20 or 80 mg QD. The latter dose is bioequivalent to a 61 mg QD dose of tafamidis free acid (Vyndamax). The tafamidis CSF concentration in ATTRv patients on 20 mg Vyndaqel is ∼125 nM. By linear extrapolation, we expect a CSF concentration of ∼500 nM at the higher dose. When tafamidis is added to healthy donor CSF at 125 or 500 nM, the WT TTR dissociation rate decreases by 42% or 87%, respectively.</p><p><strong>Conclusions: </strong>Tafamidis stabilises TTR in CSF to what is likely a clinically meaningful extent at CSF concentrations achieved by the normal tafamidis dosing regimen.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"279-289"},"PeriodicalIF":5.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10056975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neurofilament light chain as a biomarker for monitoring response to change in treatment in hereditary ATTR amyloidosis. 神经丝轻链作为监测遗传性ATTR淀粉样变治疗变化反应的生物标志物。
IF 5.5 2区 医学
Amyloid-Journal of Protein Folding Disorders Pub Date : 2023-09-01 DOI: 10.1080/13506129.2023.2187678
Mitsuto Sato, Yusuke Mochizuki, Yusuke Takahashi, Ken Takasone, Emre Aldinc, Simina Ticau, Gang Jia, Yoshiki Sekijima
{"title":"Neurofilament light chain as a biomarker for monitoring response to change in treatment in hereditary ATTR amyloidosis.","authors":"Mitsuto Sato,&nbsp;Yusuke Mochizuki,&nbsp;Yusuke Takahashi,&nbsp;Ken Takasone,&nbsp;Emre Aldinc,&nbsp;Simina Ticau,&nbsp;Gang Jia,&nbsp;Yoshiki Sekijima","doi":"10.1080/13506129.2023.2187678","DOIUrl":"https://doi.org/10.1080/13506129.2023.2187678","url":null,"abstract":"Hereditary ATTR (ATTRv) amyloidosis is a fatal autosomal dominant disorder in which variants in the transthyretin (TTR) gene cause systemic deposition of amyloid fibrils. ATTRv amyloidosis is characterised by progressive lengthdependent sensorimotor neuropathy, autonomic neuropathy, and non-neuropathic manifestations [1]. Several effective pharmacological therapies are available, including TTR tetramer stabilisers (diflunisal and tafamidis) and nucleic acid-based medications such as RNA interference therapeutics (patisiran and vutrisiran) and anti-sense oligonucleotide (inotersen) [1,2]. However, evaluation and monitoring of disease progression and treatment response are challenging in clinical practice, because existing assessment methods are not sensitive enough to detect changes in disease activity. Neurofilament light chain (NfL) is an integral component of the neurons, and has been described as a biomarker of neuroaxonal injury across several central and peripheral nervous system diseases. Additionally, recent analyses have identified NfL as a potential biomarker of neuronal injury in ATTRv amyloidosis [3,4]. In this analysis, we evaluated the value of NfL in monitoring treatment response in patients with ATTRv amyloidosis with polyneuropathy whose treatment was switched from tafamidis to patisiran. Eleven patients (10 male) with ATTRv amyloidosis with polyneuropathy who switched treatment from tafamidis (20mg oral once daily) to patisiran (0.3mg/kg IV once in every three weeks) were included. The reason for switch was worsening of polyneuropathy. Serum NfL levels of patients were measured at baseline (while receiving tafamidis, just before switch), one and two years after switch to patisiran. In eight of the eleven patients, NfL levels were available at two years following switch. Patients were also assessed for neurologic impairment with neuropathy impairment score (NIS) at baseline and one and/or two years following switch. Since the patients were assessed during routine visits, NfL and NIS measurements at 1-year and 2-year post-switch occurred within 3months of those time points, except one patient whose 2-year measurements were delayed by four months. NfL levels were measured using the QuanterixR Simoa platform. The Wilcoxon signed-rank test was used to compare NfL levels and NIS values before, and one and two years after switch to patisiran. p&lt; 0.05 was considered statistically significant. This study was approved by the Ethical Committee of Shinshu University School of Medicine (No. 4852) and written informed consent was obtained from patients. Mean (±SD) age at disease onset and study inclusion were 39.5 ± 12.6 and 46.9 ± 14.0 years, respectively. TTR variants were V30M (p.V50M) (n1⁄4 8), A36P (p.A56P), S50A (p.S70A), and I107V (p.I127V), (n1⁄4 1 each). NfL and NIS measurements at baseline were available for all 11 patients. Serum NfL levels were available for 11/11 and 8/11 patients at one and two years following switch, respectivel","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"351-352"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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