Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Left atrial strain identifies early cardiac involvement in variant transthyretin amyloidosis.","authors":"Matteo Serenelli, Elisa Gardini, Stefania Marazia, Alessandro Barbarossa, Alberto Cipriani, Anna Cantone, Beatrice Dal Passo, Federico Sanguettoli, Rita Pavasini, Matteo Arzenton, Gianluca Campo, Andrea Zaccaro, Emiliano Rossi, Gioele Fabbri, Enrico Monti, Carmine Pizzi, Erika Pedio, Federico Guerra, Giulio Sinigiani, Alberto Aimo, Michele Emdin, Francesco Cappelli, Federica Colio, Simone Longhi","doi":"10.1080/13506129.2026.2663922","DOIUrl":"https://doi.org/10.1080/13506129.2026.2663922","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-5"},"PeriodicalIF":7.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845800","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":"Accelerated apolipoprotein A-II senile amyloidosis in a plasminogen activator inhibitor-1 knock-out model.","authors":"Gilles R Codo, Pauline Duchatelet, Gemma Martinez-Rivas, Alessio Lampis, Karolina Weronika Świderska, Emilie Pinault, Camille Cohen, Magali Colombat, Sebastien Bender, Christophe Sirac","doi":"10.1080/13506129.2026.2661603","DOIUrl":"https://doi.org/10.1080/13506129.2026.2661603","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-5"},"PeriodicalIF":7.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788162","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":"Transthyretin stabilizer therapy increases naturally-occurring antibodies in ATTR cardiomyopathy.","authors":"Stephan Settelmeier, Daniel Agranovski, Maximilian Steinhardt, Sarah Waydhas, Ian Gering, Vladimir Cejka, Caroline Morbach, Stefan Störk, Dieter Willbold, Ralf Küppers, Julia Vogel, Lars Michel, Alexander Carpinteiro, H Christian Reinhardt, Richard Dodel, Tienush Rassaf, Alexander J Ross, Ulrike B Hendgen-Cotta","doi":"10.1080/13506129.2026.2651299","DOIUrl":"https://doi.org/10.1080/13506129.2026.2651299","url":null,"abstract":"<p><strong>Background: </strong>Amyloid transthyretin cardiomyopathy (ATTR-CM) results from extracellular deposition of misfolded transthyretin (TTR), causing progressive heart failure. Naturally-occurring antibodies (nAbs) targeting misfolded proteins exist in neurodegenerative disease, but their presence in ATTR-CM is unknown. The objective of this study is to determine whether nAbs against TTR (nAbs_TTR) exist in humans and whether they are influenced by disease or its treatment.</p><p><strong>Methods: </strong>Serum from healthy donors, umbilical cord blood (UCB), and patients with ATTR-CM - both untreated and receiving TTR-stabilizing therapy - was analyzed for nAbs_TTR using immunoassays, blotting, and binding studies. Functional activity was evaluated in a fibril formation assay.</p><p><strong>Results: </strong>nAbs_TTR binding both native and amyloid TTR (ATTR) with high affinity (KD 30 nM/7 nM) were detected in healthy serum and UCB. NAbs_TTR levels were significantly altered in ATTR-CM compared to controls: nAbsTTR (IgG) were higher while nAbsTTR (IgM) were lower. nAbsTTR of both subtypes significantly increased by 22% (<i>p</i> ≤ 0.05) in patients receiving TTR-stabilizing therapy. <i>In vitro</i>, nAbs_TTR suppressed TTR fibril aggregation.</p><p><strong>Conclusions: </strong>Naturally-occurring TTR-targeting antibodies are present from birth, modulated by disease and therapy, and inhibit fibril formation. These findings reveal an unrecognized immune mechanism with potential relevance for ATTR-CM pathogenesis and treatment.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-17"},"PeriodicalIF":7.4,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624552","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":"Incidence of second primary malignancies in patients with AL amyloidosis and the impact of disease stage and therapies.","authors":"Efstathios Kastritis, Vassiliki Spiliopoulou, Foteini Theodorakakou, Magdalini Migkou, Panagiotis Malandrakis, Evangelos Terpos, Maria Gavriatopoulou, Meletios Athanasios Dimopoulos","doi":"10.1080/13506129.2026.2648188","DOIUrl":"https://doi.org/10.1080/13506129.2026.2648188","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-4"},"PeriodicalIF":7.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595535","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":"Development and validation of the modified-comprehensive Kumamoto Score: a multi-organ assessment tool for hereditary transthyretin amyloidosis.","authors":"Shiori Yamakawa, Toshiya Nomura, Yohei Misumi, Tomoaki Taguchi, Keiichi Nakahara, Masayoshi Tasaki, Naoto Kuyama, Hiroki Usuku, Yasuhiro Izumiya, Yuji Takihara, Emre Aldinc, Konen Obayashi, Toshihiro Inoue, Kenichi Tsujita, Yukio Ando, Mitsuharu Ueda","doi":"10.1080/13506129.2026.2649884","DOIUrl":"https://doi.org/10.1080/13506129.2026.2649884","url":null,"abstract":"<p><strong>Background: </strong>Disease-modifying therapies for hereditary transthyretin (ATTRv) amyloidosis necessitate sensitive, multi-organ assessment tools capturing early disease manifestations across heterogeneous phenotypes. We developed and validated the modified-comprehensive Kumamoto Score (mKS).</p><p><strong>Methods: </strong>This prospective validation study enrolled 76 genetically confirmed ATTRv amyloidosis patients. The mKS comprises four organ-specific subscales: peripheral neuropathy (mKS-PN, 0-258), cardiomyopathy (mKS-CM, 0-195), eye (mKS-E, 0-60) and central nervous system (CNS) involvement (mKS-CNS, 0-45); total range 0-558. Construct validity was primarily assessed through Spearman's correlations with established clinical scores, objective biomarkers and patient-reported quality of life.</p><p><strong>Results: </strong>The median patient age was 56.2 years; 60.5% had Val30Met (p.Val50Met) mutations. The mKS demonstrated strong validity with established scores (Kumamoto Score (KS): <i>ρ</i> = 0.798; Neuropathy Impairment Score (NIS): <i>ρ</i> = 0.791; both <i>p</i> < .001) and quality of life (EuroQol 5-Dimension 5-Level (EQ-5D-5L): <i>ρ</i> = -0.731, <i>p</i> < .001). Organ-specific subscales demonstrated strong construct validity: mKS-PN correlated strongly with NIS (<i>ρ</i> = 0.906) and neurophysiological parameters (peroneal CMAP (compound muscle action potential): <i>ρ</i> = -0.819; tibial CMAP: <i>ρ</i> = -0.801); mKS-CM correlated strongly with cardiac biomarkers (B-type natriuretic peptide, BNP: <i>ρ</i> = 0.776; high-sensitivity troponin T (hs-TnT): <i>ρ</i> = 0.712) and imaging parameters (extracellular volume fraction (ECV): <i>ρ</i> = 0.743; interventricular septum thickness in diastole (IVSTd): <i>ρ</i> = 0.716). Subscale intercorrelations were weak (<i>ρ</i> = 0.155-0.381), confirming independent organ assessment.</p><p><strong>Conclusions: </strong>The mKS provides a validated comprehensive assessment tool for ATTRv amyloidosis with enhanced early-stage sensitivity and independent organ-specific subscales, addressing critical unmet needs in the era of disease-modifying therapies.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-11"},"PeriodicalIF":7.4,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596129","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":"Serum peripherin as a disease biomarker in hereditary transthyretin amyloidosis: a multicenter cohort study.","authors":"Domenico Plantone, Delia Righi, Angela Romano, Luca Leonardi, Valeria Guglielmino, Francesca Forcina, Marco Ceccanti, Maurizio Inghilleri, Fiore Manganelli, Stefano Tozza, Maria Ausilia Sciarrone, Francesca Vitali, Andrea Sabino, Carlo Manco, Angela Stufano, Maria Laura Stromillo, Nicola De Stefano, Paolo Calabresi, Guido Primiano, Marco Luigetti","doi":"10.1080/13506129.2026.2640984","DOIUrl":"https://doi.org/10.1080/13506129.2026.2640984","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a rare, progressive, and fatal multisystemic disease. Peripherin represents a promising biomarker for axonal damage in the peripheral nervous system (PNS). This study aims to investigate serum peripherin levels in symptomatic and presymptomatic ATTRv subjects, alongside serum neurofilament light chain (sNfL) levels, and their correlations with disease progression and severity.</p><p><strong>Methods: </strong>This multicenter, cross-sectional cohort study included 96 individuals with <i>TTR</i> gene variants (49 presymptomatic and 47 symptomatic ATTRv subjects) and 42 healthy controls (HCs). Serum peripherin levels were measured using a highly sensitive homebrew immunoassay, whereas sNfL levels were determined using a commercially available Simoa Neurology 2-Plex B assay. Statistical analyses included non-parametric Spearman correlations, Kruskal-Wallis ANOVA, ANCOVA, and binomial logistic regression.</p><p><strong>Results: </strong>Serum peripherin levels were elevated in both presymptomatic (<i>p</i> < 0.001) and symptomatic ATTRv groups (<i>p</i> < 0.001) compared to HCs. Peripherin levels did not correlate with age, sNfL levels, or clinical severity, but showed a strong discriminative ability between ATTRv and HCs (AUC = 0.83, sensitivity = 76%, specificity = 76%, <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>This study demonstrates that serum peripherin represents a promising biomarker for early detection of PNS damage in ATTRv, with elevated levels detectable even in presymptomatic stages.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-10"},"PeriodicalIF":7.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470225","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 impact of lilac-colored aggregates on may-Grünwald-Giemsa-stained bone marrow smears in patients with amyloid light-chain amyloidosis.","authors":"Ayaka Kodama, Ritsuko Nakagoshi, Ryuto Oshita, Suzuho Onagi, Satoshi Fujimura, Yuka Takezawa, Nagaaki Katoh, Yoshiki Sekijima, Masahide Yazaki, Yumiko Higuchi","doi":"10.1080/13506129.2026.2639830","DOIUrl":"https://doi.org/10.1080/13506129.2026.2639830","url":null,"abstract":"<p><strong>Background: </strong>Lilac-colored aggregates (LicAGs) are often observed on bone marrow (BM) aspirate smears stained with May-Grünwald-Giemsa (MG) in patients with amyloid light-chain (AL) amyloidosis. However, the clinicopathological features of LicAGs observed on MG-stained BM smears remain poorly understood.</p><p><strong>Methods: </strong>We examined MG-stained BM aspirate smears and clinical data from 103 patients with AL amyloidosis. To determine whether LicAGs represented amyloid, LicAG-positive specimens were decolorized, re-stained with Congo red, and examined under polarized light. Patients were grouped based on the presence or absence of LicAGs, and their clinical characteristics were compared. Serial changes in LicAG counts following therapy were assessed in two cases.</p><p><strong>Results: </strong>Of the 103 patients, 20 showed LicAGs (BM[+] group), confirmed as amyloid fibrils using Congo red staining. Compared to the BM(-) group, the BM(+) group had higher proportions of κ-type amyloid, liver and tongue involvement, and negative monoclonal immunoglobulin on immunofixation electrophoresis. LicAG counts decreased on serial BM examinations in two patients after treatment.</p><p><strong>Conclusions: </strong>LicAGs are amyloid fibrils, indicating their potential significance in AL amyloidosis, especially when monoclonal immunoglobulins are undetectable. They may also serve as indicators of organ involvement and as surrogate markers for treatment response.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-10"},"PeriodicalIF":7.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379479","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":"Lysozyme encounters transthyretin: rethinking amyloid complexity in ligamentum flavum.","authors":"Mitsuharu Ueda","doi":"10.1080/13506129.2026.2640976","DOIUrl":"https://doi.org/10.1080/13506129.2026.2640976","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-2"},"PeriodicalIF":7.4,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379474","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":"Systemic fibrinogen Aα-chain amyloidosis in Manchester Terrier dogs.","authors":"Natsumi Kobayashi, Keiichi Kuroki, Yoshiyuki Itoh, Tomoaki Murakami","doi":"10.1080/13506129.2026.2637775","DOIUrl":"https://doi.org/10.1080/13506129.2026.2637775","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-4"},"PeriodicalIF":7.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357329","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":"Early cardiac sympathetic denervation in hereditary transthyretin amyloidosis: ¹²³I-metaiodobenzylguanidine findings and correlation with skin biopsy.","authors":"Viviana Frantellizzi, Chiara Cambieri, Eleonora Galosi, Cristina Chimenti, Giulia Marchionni, Maria Alfarano, Federico Ballatore, Jacopo Costantino, Marco Luigetti, Maria Ausilia Sciarrone, Francesca Graziani, Luca Leonardi, Maria Beatrice Musumeci, Laura Libonati, Federica Moret, Matteo Di Giulio, Matteo Garibaldi, Francesca Forcina, Andrea Truini, Maria Silvia De Feo, Giuseppe De Vincentis, Maurizio Inghilleri, Marco Ceccanti","doi":"10.1080/13506129.2026.2636657","DOIUrl":"https://doi.org/10.1080/13506129.2026.2636657","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis (ATTRv) is a multisystem disorder caused by misfolded TTR deposition, leading to neuropathy and cardiomyopathy. Early identification of subclinical involvement remains difficult. We evaluated cardiac sympathetic innervation and small fiber neuropathy in symptomatic patients and asymptomatic carriers (AC) using ¹²³I-metaiodobenzylguanidine (¹²³I-mIBG) scintigraphy, skin biopsy and nerve conduction studies to assess cutaneous silent period (CSP).</p><p><strong>Methods: </strong>In this cross-sectional study, 14 symptomatic patients, 18 AC and 32 healthy controls (HC) underwent ¹²³I-mIBG imaging to determine early and late heart-to-mediastinum ratios (e-H/M, l-H/M) and summed scores (ESS, LSS). Skin biopsies quantified intraepidermal (IENFD) and piloerector muscle nerve fiber density (PMNFD) in upper and lower limbs. Cutaneous silent period (CSP) assessed A-δ fiber function. Correlations between ¹²³I-mIBG and years from predicted age of disease onset (delta-PADO) were analyzed in AC.</p><p><strong>Results: </strong>l-H/M was reduced in AC versus HC (1.73 ± 0.23 vs 1.94 ± 0.19; <i>p</i> < 0.05) and further in patients (1.37 ± 0.25; <i>p</i> < 0.01). Delta-PADO correlated with e-H/M (<i>p</i> < 0.05), ESS (<i>p</i> < 0.01) and LSS (<i>p</i> < 0.01). Half of AC showed reduced lower-limb IENFD. CSP latencies were prolonged or absent in advanced cases.</p><p><strong>Conclusion: </strong>Reduced l-H/M indicates early cardiac sympathetic denervation in AC, preceding clinical symptoms. Combined ¹²³I-mIBG and skin biopsy improves early detection and risk stratification in ATTRv.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-13"},"PeriodicalIF":7.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345684","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}