Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Computed tomography-derived myocardial radiomics for detection of transthyretin amyloidosis in patients with severe aortic stenosis.","authors":"Alexios S Antonopoulos, Ioannis Panagiotopoulos, Konstantinos Karampinos, Konstantinos Spargias, Charalampos Papastamos, Theodoros Tsampras, Nikolaos Axypolitos, Spyridon Simantiris, Georgios Benetos, Nikolaos Ktenopoulos, Panagiotis Kanatas, Maria Koutelou, Konstantinos Toutouzas, Marios Ioannides, Christos Eftychiou, Christos Mourmouris, Thomas Vrachliotis, Charalambos Antoniades, Konstantinos Tsioufis, Charalambos Vlachopoulos","doi":"10.1080/13506129.2025.2486072","DOIUrl":"https://doi.org/10.1080/13506129.2025.2486072","url":null,"abstract":"<p><strong>Background: </strong>We explored the value of myocardial radiomics by computed tomography angiography (CTA) for detection of transthyretin amyloidosis cardiomyopathy (ATTR-CM).</p><p><strong>Methods: </strong>The study included 589 patients with aortic stenosis and CTA datasets. Radiomics were extracted from LV myocardium. Arm 1 (<i>n</i> = 400) served for method optimisation and removal of redundant features. In Arm 2 (<i>n</i> = 30), we identified radiomics associated with extracellular volume by CT (ECV_CT); in Arm 3 (<i>n</i> = 159), radiomics were compared in patients with/without positive bone scintigraphy scan (training cohort, <i>n</i> = 84; validation cohort, <i>n</i> = 75) to build a radiomic signature for ATTR-CM.</p><p><strong>Results: </strong>In Arm 1, unsupervised clustering of patients based on radiomics was associated with significant differences in patients' clinical profile among clusters. In Arm 2, we constructed a radiomic-based ECV (correlation with ECV_CT: rho = .78, <i>p</i> = 1.2 x 10^-6) with excellent diagnostic accuracy for high ECV_CT (AUC = .925, 95%CI: .825-1.000, <i>p</i> = .0002). In Arm 3, a radiomic score (AmyloidRS) had good performance for ATTR-CM detection in the training (c-index .88, 95%CI: .80-.95) and validation cohort (c-index .84, 95%CI: .69-.98). When combined with clinical features, AmyloidRS maximised diagnostic accuracy for ATTR (kappa: .894, balanced accuracy .984).</p><p><strong>Conclusions: </strong>We present a radiomic method for myocardial tissue characterisation in patients with severe aortic stenosis which enables ATTR-CM detection from standard CTA scans.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-12"},"PeriodicalIF":5.2,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797143","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}

{"title":"Abnormal global longitudinal strain and reduced serum inflammatory markers in cardiac AL amyloidosis patients without significant amyloid fibril deposition.","authors":"Camille V Edwards, Grace M Ferri, Josue Villegas-Galaviz, Sabrina Ghosh, Pushpinder Singh Bawa, Feiya Wang, Elena Klimtchuk, Tinuola B Ajayi, Gareth J Morgan, Tatiana Prokaeva, Andrew Staron, Frederick L Ruberg, Vaishali Sanchorawala, Richard M Giadone, George J Murphy","doi":"10.1080/13506129.2025.2478397","DOIUrl":"https://doi.org/10.1080/13506129.2025.2478397","url":null,"abstract":"<p><strong>Background: </strong>Cardiac dysfunction in AL amyloidosis is thought to be partly related to the direct impact of AL LCs on cardiomyocyte function, with the degree of dysfunction at diagnosis as a major determinant of clinical outcomes. Nonetheless, mechanisms underlying LC-induced myocardial toxicity remain unclear.</p><p><strong>Methods: </strong>We identified gene expression changes correlating with human cardiac cell exposure to cardiomyopathy-associated AL LCs. We then confirmed these findings in a clinical dataset focusing on clinical parameters associated with pathways dysregulated at the gene expression level.</p><p><strong>Results: </strong>Upon exposure to cardiomyopathy-associated AL LCs, cardiac cells exhibited gene expression changes related to myocardial contractile function and inflammation, leading us to hypothesise that there could be clinically detectable changes in global longitudinal strain (GLS) on echocardiogram and serum inflammatory markers in patients. Thus, we identified 29 patients with normal interventricular septum diameter (IVSd) but abnormal cardiac biomarkers, suggestive of LC-induced cardiac dysfunction. These patients display early cardiac biomarker staging, abnormal GLS, and significantly reduced serum inflammatory markers compared to patients with clinically evident amyloid fibril deposition.</p><p><strong>Conclusion: </strong>Collectively, our findings highlight early molecular and functional signatures of cardiac AL amyloidosis, with potential impact for developing improved patient biomarkers and novel therapeutics.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-14"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711935","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}

{"title":"Cardiac amyloidosis after lumbar spinal stenosis surgery - a comprehensive prospective cohort study.","authors":"Per Eldhagen, Antonios Tzortzakakis, Lars H Lund, Liselott Söderström, Svante Berg, Per Westermark, Peder Sörensson","doi":"10.1080/13506129.2025.2481310","DOIUrl":"https://doi.org/10.1080/13506129.2025.2481310","url":null,"abstract":"<p><strong>Background: </strong>Wild-type transthyretin (ATTRwt) amyloidosis is underdiagnosed and generally diagnosed with manifest cardiac involvement. Lumbar spinal stenosis (LSS) might be an early sign of systemic transthyretin amyloidosis and a possible screening target for early diagnosis.</p><p><strong>Objectives: </strong>To assess the prevalence of cardiac amyloidosis (CA) 6 years post-LSS surgery, among patients with transthyretin amyloid deposits in ligamentum flavum.</p><p><strong>Methods: </strong>Twenty-one patients who had surgery for LSS in 2016-2018 and grade 3-4 ATTR amyloid deposits in ligamentum flavum were followed up in 2022-2023, including biomarkers, echocardiography, cardiac magnetic resonance (CMR) and nuclear imaging.</p><p><strong>Results: </strong>At follow-up, median age was 79 years, 16% (3/19) displayed cardiac uptake on scintigraphy consistent with ATTR-CA. Forty-eight percent (10/21) had a history of other tenosynovial conditions associated with ATTRwt. We observed a small increase in tissue characteristics using CMR, and a decrease in left ventricular global longitudinal strain and left atrial strain on echocardiography.</p><p><strong>Conclusions: </strong>In this prospective cohort study, 16% were diagnosed with ATTRwt cardiomyopathy, six years following surgery for LSS. History of other tenosynovial conditions associated with ATTRwt amyloidosis was common. These findings strengthen the hypothesis that LSS is a possible manifestation of ATTRwt amyloidosis and that in selected patients with LSS, cardiac follow-up is of value.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-8"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711936","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}

{"title":"Multigene panel analysis has limited additional value compared to transthyretin gene analysis in Dutch patients with suspected cardiac amyloidosis.","authors":"Milou Berends, Hendrea S A Tingen, Johan Bijzet, Henny H Lemmink, Friso L H Muntinghe, Ewout J Houwerzijl, Peter van der Meer, Riemer H J A Slart, Janet A Gilbertson, Reinold O B Gans, Bouke P C Hazenberg, Hans L A Nienhuis, Paul A van der Zwaag","doi":"10.1080/13506129.2025.2469609","DOIUrl":"https://doi.org/10.1080/13506129.2025.2469609","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-4"},"PeriodicalIF":5.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598214","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}

{"title":"Complete remission after patisiran treatment in a patient with nephrotic syndrome secondary to hereditary transthyretin amyloidosis (ATTR).","authors":"Axel Vila, Anissa Moktefi, Thibaud Damy, Violaine Planté-Bordeneuve, Philippe Remy, Magali Colombat, Vincent Audard, Hamza Sakhi","doi":"10.1080/13506129.2025.2472819","DOIUrl":"https://doi.org/10.1080/13506129.2025.2472819","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-4"},"PeriodicalIF":5.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568289","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}

{"title":"Whole tissue proteomic analyses of cardiac ATTR and AL unveil mechanisms of tissue damage.","authors":"Brian C Netzel, M Cristine Charlesworth, Kenneth L Johnson, Amy J French, Angela Dispenzieri, Joseph J Maleszewski, Ellen D McPhail, Martha Grogan, Margaret M Redfield, Megan Weivoda, Eli Muchtar, Morie A Gertz, Shaji K Kumar, Pinaki Misra, Julie Vrana, Jason Theis, Suzanne R Hayman, Marina Ramirez-Alvarado, Surendra Dasari, Taxiarchis Kourelis","doi":"10.1080/13506129.2024.2448440","DOIUrl":"10.1080/13506129.2024.2448440","url":null,"abstract":"<p><strong>Background: </strong>Cardiac AL and ATTR are potentially fatal cardiomyopathies. Current therapies do not address mechanisms of tissue dysfunction because these remain unknown. Our prior work focused on the amyloid plaque proteome, which may not capture tissue-wide proteomic alterations.</p><p><strong>Objectives: </strong>To evaluate mechanisms of tissue dysfunction in cardiac AL and ATTR using a full biopsy tissue proteomics approach.</p><p><strong>Methods: </strong>We performed proteomics analysis on 76 ATTR and 27 AL diagnostic endomyocardial biopsies.</p><p><strong>Results: </strong>Stage-3 AL patients exhibited increased coagulation, extracellular matrix remodelling (ECM), epithelial-to-mesenchymal transition (EMT), complement activation, hypoxia, and clathrin-mediated endocytosis pathways <i>vs.</i> stages-1/2, with decreased healthy cardiac metabolism. In stages-2 and 3 ATTR, immunoglobulin proteins, complement, and keratinisation pathways were increased compared to stage-1. Unsupervised analyses identified an ATTR group with worse survival characterised by upregulated complement and downregulated metabolic pathways. Compared to ATTR, AL had higher clathrin-mediated endocytosis, mRNA splicing, and ribosomal proteins, while ATTR had higher complement levels.</p><p><strong>Conclusions: </strong>This study identifies known processes dysregulated in heart failure with preserved ejection fraction as well as novel pathways responsible for tissue damage. Our results support an immune-mediated mechanism of tissue toxicity in cardiac amyloidosis, especially among patients with worse outcomes.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"72-80"},"PeriodicalIF":5.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958446","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}

{"title":"AA amyloidosis in vertebrates: epidemiology, pathology and molecular aspects.","authors":"Valentina Moccia, Claudia Maria Tucciarone, Silvia Garutti, Melissa Milazzo, Filippo Ferri, Carlo Palizzotto, Maria Mazza, Marco Basset, Eric Zini, Stefano Ricagno, Silvia Ferro","doi":"10.1080/13506129.2024.2417219","DOIUrl":"10.1080/13506129.2024.2417219","url":null,"abstract":"<p><p>AA amyloidosis is a prototypic example of systemic amyloidosis: it results from the prolonged overproduction of SAA protein produced in response to chronic inflammation. AA amyloidosis primarily affects the kidneys, liver, spleen, gastrointestinal tract, leading to a variety of symptoms. First, this review examines AA amyloidosis in humans, focusing on pathogenesis, clinical presentation, and diagnosis and then in animals. In fact AA amyloidosis is the only systemic amyloidosis that has been largely documented in a remarkable number of vertebrate species: mammals, birds, and fishes, especially in individuals with comorbidities, chronic stress, or held in captivity. Secondly, here, we summarise independent sets of evidence obtained on different animal species, exploring the possible transmissibility of AA amyloidosis especially in crowded or confined populations. Finally, biochemical and structural data on native SAA and on AA amyloid fibrils from human, murine, and cat ex vivo samples are discussed. The available structural data depict a complex scenario, where SAA can misfold forming highly different amyloid assemblies. This review highlights the complexity of AA amyloidosis, emphasising the need for further research into its spread in the animal kingdom, its structural aspects, and pathogenetic mechanisms to evaluate its impact on human and animal health.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"3-13"},"PeriodicalIF":5.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480034","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}

{"title":"PRX004 in variant amyloid transthyretin (ATTRv) amyloidosis: results of a phase 1, open-label, dose-escalation study.","authors":"Ole B Suhr, Martha Grogan, Ana Martins da Silva, Chafic Karam, Pablo Garcia-Pavia, Brian Drachman, Wagner Zago, Radhika Tripuraneni, Gene G Kinney","doi":"10.1080/13506129.2024.2420809","DOIUrl":"10.1080/13506129.2024.2420809","url":null,"abstract":"<p><strong>Background: </strong>The investigational monoclonal antibody PRX004 is designed to specifically target and deplete TTR amyloid. Here, we report on the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical activity of PRX004 in patients with ATTRv amyloidosis.</p><p><strong>Methods: </strong>This global, multicentre, phase 1 trial comprised a 3 + 3 dose-escalation phase and a long-term extension (LTE) phase (NCT03336580). In the dose-escalation phase, patients received PRX004 (0.1, 0.3, 1, 3, 10 or 30 mg/kg), administered intravenously every 28 days for 3 months. In the LTE, eligible patients could receive up to 15 additional doses. Patients who received doses of ≥3 mg/kg for ≥9 months were assessed for Global Longitudinal Strain (GLS) and Neuropathy Impairment Score (NIS). The primary objective was to determine the maximum tolerated dose (MTD) of PRX004.</p><p><strong>Results: </strong>Overall, 21 patients with ATTRv amyloidosis completed the dose-escalation phase; 17 subsequently enrolled in the LTE. The MTD was not reached. PRX004 was well tolerated at all doses, with dose-proportional exposure. GLS and NIS were improved or maintained over 9 months (<i>n</i> = 7).</p><p><strong>Conclusions: </strong>PRX004 was well tolerated in patients with ATTRv amyloidosis and demonstrated potential clinical activity. A phase 2 randomised controlled trial in ATTR cardiomyopathy is ongoing (NCT05442047).</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"14-21"},"PeriodicalIF":5.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548803","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}

{"title":"Clinical and genetic features of AGel amyloidosis caused by novel gelsolin variant and its impact on cardiac function and conduction disorders.","authors":"A Roldán-Sevilla, M Gallego-Delgado, M T Lista-Araujo, J Torres-Pérez, A M Merino-Merino, C Gil-Polo, D Cantero-Lozano, S M Lorenzo-Hernandez, R Eiros-Bachiller","doi":"10.1080/13506129.2024.2441784","DOIUrl":"10.1080/13506129.2024.2441784","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"90-92"},"PeriodicalIF":5.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856388","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}

{"title":"Effects of eplontersen on symptoms of autonomic neuropathy in hereditary transthyretin-mediated amyloidosis: secondary analysis from the NEURO-TTRansform trial.","authors":"Jonas Wixner, John L Berk, David Adams, Michael Polydefkis, Isabel Conceição, Shahram Attarian, Julian D Gillmore, P James B Dyck, Folke Folkvaljon, Wunan Zhou, Jersey Chen, Nicholas J Viney, T Jesse Kwoh, Teresa Coelho, Márcia Waddington-Cruz","doi":"10.1080/13506129.2024.2427290","DOIUrl":"10.1080/13506129.2024.2427290","url":null,"abstract":"<p><strong>Background: </strong>The NEURO-TTRansform trial showed that after 66 weeks of treatment, eplontersen significantly reduced neuropathic impairment and improved quality of life (QoL) in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN). In this secondary analysis from NEURO-TTRansform, autonomic impairment, and the impact of eplontersen on autonomic impairment progression was evaluated through 85 weeks in patients randomised to eplontersen (<i>n</i> = 144) versus external placebo (<i>n</i> = 60; through Week 66 from the NEURO-TTR trial).</p><p><strong>Methods: </strong>Change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) composite score, Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) total score, and the Neuropathy Symptoms and Change (NSC) total score was evaluated. Exploratory assessments were change in autonomic components of these instruments, Composite Autonomic Symptom Score-31 (COMPASS-31) total score, and nutritional status (modified body mass index [mBMI]).</p><p><strong>Results: </strong>Patients reported profound autonomic dysfunction at baseline. Improvements with eplontersen versus placebo were observed up to Week 66 in autonomic components of mNIS+7, Norfolk QoL-DN, NSC, and mBMI; eplontersen results were sustained up to Week 85, including improvements in COMPASS-31 (Week 81).</p><p><strong>Conclusions: </strong>Eplontersen demonstrated benefit across multiple measures of autonomic impairment known to progress rapidly and negatively impact QoL without treatment, without deterioration in nutritional status.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"29-38"},"PeriodicalIF":5.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649726","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}