Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Gastric amyloid pathology and mucosal denervation in ATTRv amyloidosis: insights from patients, mice, and gut microenvironment profiles.","authors":"Hsueh-Wen Hsueh, Ping-Hao Yang, Ping-Huei Tseng, Ti-Yen Yeh, Hao-Chia Hsu, Chieh-Chang Chen, Chia-Lang Hsu, Ya-Yin Cheng, Tsai-Wei Ting, Cheng-Chen Lin, Hui-Fang Ke, Ching-Hua Kuo, Chi-Chao Chao, Koping Chang, Sung-Tsang Hsieh","doi":"10.1080/13506129.2026.2723933","DOIUrl":"https://doi.org/10.1080/13506129.2026.2723933","url":null,"abstract":"<p><strong>Backgrounds: </strong>Hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) frequently presents with gastrointestinal autonomic dysfunction, but its underlying pathology remains unclear.</p><p><strong>Methods: </strong>We examined gastric mucosal amyloid deposition and innervation using conventional endoscopic biopsies in ATTRv-PN patients and a human TTR (hTTR A117S) knock-in mouse model. Clinical assessments, gut microbiota, metabolomics, and neurite growth assays were integrated.</p><p><strong>Results: </strong>Among 33 patients, 84.8% showed TTR(+) amyloid deposition in gastric mucosa. Gastric mucosal innervation density (GMID) was significantly reduced in all gastric regions compared with controls and was similarly decreased in hTTR(A117S) mice. Lower GMID correlated with gastroparesis and reflux symptom severity. Integrated analyses revealed positive associations between GMID, four microbial genera, and histidine levels. Both microbiota-derived principal components and histidine independently correlated with GMID. Histidine also promoted neurite growth <i>in vitro</i>.</p><p><strong>Conclusions: </strong>Endoscopic biopsy enables assessment of both gastric amyloid pathology and mucosal innervation in ATTRv-PN. Reduced GMID is closely associated with gastrointestinal symptoms, microbiota alterations, and metabolomic changes, providing insights into disease mechanisms and potential biomarkers of autonomic gastrointestinal dysfunction.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-14"},"PeriodicalIF":5.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857812","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":"Hereditary ATTR amyloidosis with prominent central nervous system involvement associated with the p.Arg54Gly (Arg34Gly) substitution.","authors":"Consuelo Ciprietti, Mirella Russo, Giuliano F Patanè, Loris Di Clemente, Gaetano Polito, Sara Melchiorre, Lorenzo Salvatorelli, Fedele Dono, Astrid Thomas, Stefano L Sensi","doi":"10.1080/13506129.2026.2719698","DOIUrl":"https://doi.org/10.1080/13506129.2026.2719698","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-5"},"PeriodicalIF":5.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820138","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":"Selective cellular vulnerability and resilience in amyloidosis: insights from the 2025 International Society of Amyloidosis Workshop.","authors":"Giampaolo Merlini","doi":"10.1080/13506129.2026.2714521","DOIUrl":"10.1080/13506129.2026.2714521","url":null,"abstract":"<p><strong>Background: </strong>Amyloidosis is characterized by hierarchical organ-specific targeting related to the nature and amino acid sequence of the precursor protein. However, several crucial aspects of tissue vulnerability and resilience to amyloid deposition and toxicity remain poorly defined.</p><p><strong>Results: </strong>The amino acid sequence of the amyloid protein is a primary determinant of organ targeting. Cryo-electron microscopy reveals common fibril architectures across organs, indicating interactions with shared tissue constituents. The interaction with the microenvironment, comprising glycosaminoglycans, collagen, endoproteases, and tissue cells, may underlie tissue vulnerability. Cellular interactions involve internalization of amyloid precursors, leading to lysosomal dysfunction, mitochondrial impairment, reactive oxygen species production, and proteotoxicity, particularly in cardiomyocytes and mesangial cells. Increased structural dynamics in amyloidogenic light chains promote improper interactions with cell constituents. Tissue-specific proteostasis capacity declines with age, contributing to tissue vulnerability in elderly patients. Parallels with neurodegenerative diseases underscore selective cellular susceptibility due to proteostatic overload and metabolic stress.</p><p><strong>Conclusions: </strong>Evidence shows that the amino acid sequence of the amyloid protein, microenvironmental factors, and cell-intrinsic and extracellular proteostatic capacity jointly determine tissue vulnerability and resilience in amyloidosis, with relative contributions varying by amyloid protein. Identifying key determinants provides actionable targets for improving the care of systemic and localized amyloidosis.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-8"},"PeriodicalIF":5.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726225","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 significance of gastric food residue in gastrointestinal hereditary transthyretin amyloidosis.","authors":"Takuma Okamura, Yugo Iwaya, Nagaaki Katoh, Yoshiki Sekijima, Hiroyoshi Ota, Tadanobu Nagaya","doi":"10.1080/13506129.2026.2711435","DOIUrl":"https://doi.org/10.1080/13506129.2026.2711435","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin (ATTRv) amyloidosis is a systemic disorder caused by extracellular deposition of transthyretin-derived amyloid fibrils. Although gastrointestinal involvement is common, its endoscopic characteristics remain unclear. This study aimed to elucidate the endoscopic and histological features of gastrointestinal ATTRv amyloidosis.</p><p><strong>Methods: </strong>Between January 2012 and August 2024, 123 patients with histologically and genetically confirmed gastrointestinal ATTRv amyloidosis who underwent esophagogastroduodenoscopy were retrospectively enrolled (GI ATTRv group). As controls, 123 age- and sex-matched individuals without amyloidosis were included.</p><p><strong>Results: </strong>The GI ATTRv group comprised 77 men (62.6%) with a median age of 54 years. Amyloid deposition was most frequently observed in the muscularis mucosae (83.7%). More than half of both groups showed no abnormal endoscopic findings in the stomach (GI ATTRv: 61.8%, control: 62.6%; <i>p</i> = 1) or duodenum (GI ATTRv: 89.4%, control: 95.9%; <i>p</i> = .099). Gastric food residue was significantly more frequent in the GI ATTRv group than in controls (15.4% vs. 0.8%, <i>p</i> < .001).</p><p><strong>Conclusions: </strong>Gastrointestinal ATTRv amyloidosis was characterized by a lack of specific endoscopic abnormalities. However, gastric food residue may represent a useful indicator of gastrointestinal dysmotility in ATTRv amyloidosis.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-10"},"PeriodicalIF":5.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671239","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":"Diagnostic utility of deep excisional skin biopsy including abdominal fat for transthyretin cardiac amyloidosis.","authors":"Kohei Honda, Ikoi Omatsu, Tetsuhiro Yamano, Hironobu Naiki, Ayano Maruyama, Yukiko Morinaga, Noriyuki Tanaka, Aya Miyagawa-Hayashino","doi":"10.1080/13506129.2026.2711143","DOIUrl":"https://doi.org/10.1080/13506129.2026.2711143","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-4"},"PeriodicalIF":5.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622403","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":"Fewer gastrointestinal events with vutrisiran versus placebo in patients with transthyretin amyloidosis with cardiomyopathy: analysis from the phase 3 HELIOS-B study.","authors":"Marcus A Urey, Quan M Bui, Laura Obici, Jonas Wixner, Erwan Donal, Hiroaki Kitaoka, Ainara Lozano-Bahamonde, Shaun Bender, Katherine L Boyle, Emre Aldinc, Caroline Morbach","doi":"10.1080/13506129.2026.2695367","DOIUrl":"https://doi.org/10.1080/13506129.2026.2695367","url":null,"abstract":"<p><strong>Background: </strong>Patients with transthyretin amyloidosis (ATTR) with cardiomyopathy (CM) can experience extracardiac manifestations, including gastrointestinal (GI) manifestations that negatively impact their quality of life.</p><p><strong>Methods: </strong>In the double-blind HELIOS-B study, patients received vutrisiran 25 mg or placebo every 12 weeks for up to 36 months. Reported adverse events classified using preferred terms of the MedDRA GI disorders system organ class were compared between treatment arms in the overall population, the monotherapy population (not receiving tafamidis at baseline) and the baseline tafamidis subgroup.</p><p><strong>Results: </strong>Overall, 271/654 patients experienced 529 GI events, 195 in the vutrisiran arm (23.4 events per 100 patient-years) and 334 in the placebo arm (40.6 events/100 patient-years; rate ratio, 0.58; <i>p</i> < 0.0001). With vutrisiran, lower rates were observed for almost all GI events including constipation, diarrhea, nausea, abdominal pain and vomiting, versus placebo, with rates of overall GI events reduced by 38-49% across populations (all <i>p</i> < 0.0001). Reductions in mean cumulative GI events with vutrisiran versus placebo were observed from Month 3.</p><p><strong>Conclusions: </strong>Treatment with vutrisiran was associated with substantially fewer GI events versus placebo in patients with ATTR-CM, with the difference beginning early in treatment. Future trials should consider assessment of extracardiac manifestations.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-12"},"PeriodicalIF":5.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474200","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":"Progressive leptomeningeal involvement on gadolinium-enhanced FLAIR MRI in hereditary transthyretin amyloidosis with the V30M (p.V50M) mutation.","authors":"Yohei Misumi, Toshiya Nomura, Tomoaki Taguchi, Shiori Yamakawa, Hiroyuki Uetani, Masayoshi Tasaki, Konen Obayashi, Taro Yamashita, Toshinori Hirai, Yukio Ando, Mitsuharu Ueda","doi":"10.1080/13506129.2026.2702928","DOIUrl":"https://doi.org/10.1080/13506129.2026.2702928","url":null,"abstract":"<p><strong>Background: </strong>Advances in disease-modifying therapies for hereditary transthyretin (ATTRv) amyloidosis have improved long-term survival. As a result, central nervous system (CNS) involvement, particularly leptomeningeal amyloidosis and cerebral amyloid angiopathy, is increasingly encountered in V30M (p.V50M) patients. However, the frequency, distribution, and progression of CNS involvement on MRI remain unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed patients with ATTR V30M amyloidosis who underwent brain MRI with gadolinium-enhanced FLAIR (Gd-FLAIR) or susceptibility-weighted imaging (SWI) between 2010 and 2025. Associations between leptomeningeal enhancement, cerebral microbleeds, and clinical parameters were evaluated.</p><p><strong>Results: </strong>Leptomeningeal enhancement on Gd-FLAIR was observed in 13/44 patients (29.5%); disease duration was longer in patients with enhancement than in those without (15.0 [8.9-22.8] vs. 5.2 [2.4-10.5] years, <i>p</i> < 0.001). The semiquantitative Gd-FLAIR score correlated with disease duration (<i>r_s</i> = 0.56, <i>p</i> < 0.001). In contrast, cerebral microbleeds were not associated with disease duration or progression. Leptomeningeal enhancement appeared as focal surface lesions in early stages and became diffuse in advanced stages, predominantly involving the posterior fossa.</p><p><strong>Conclusions: </strong>Leptomeningeal enhancement on Gd-FLAIR MRI is a frequent and progressive finding associated with disease duration and may precede cerebral microbleeds, supporting its role as an early and sensitive marker in ATTR V30M amyloidosis.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-9"},"PeriodicalIF":5.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474169","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":"Hepatic multimodal phenotyping in AL amyloidosis with cardiac involvement: the D-Amy-LIPHE study.","authors":"Anna Sessa, Amira Zaroui, Margaux Charles, Stefano Caruso, Julien Calderaro, Jeremy Augustin, Mounira Kharoubi, François Lemonnier, Karim Belhadj, Xue Shaodian, Sébastien Mulé, Emmanuel Itti, Thibaud Damy, Vincent Leroy","doi":"10.1080/13506129.2026.2694403","DOIUrl":"https://doi.org/10.1080/13506129.2026.2694403","url":null,"abstract":"<p><strong>Background: </strong>In light-chain (AL) amyloidosis, liver involvement is defined using arbitrary criteria such as hepatomegaly or elevated Alkaline Phosphatase (ALP). We aimed to determine its prevalence and to characterize its phenotype and prognostic impact.</p><p><strong>Methods: </strong>This study included 200 patients with AL amyloidosis. Liver involvement was defined by MRI/CT hepatomegaly and/or elevated ALP. Liver phenotyping included early-phase ^99mTc-HMDP bone scintigraphy (BS), and histological analysis (<i>n</i> = 12). Predictors of liver involvement were identified using logistic regression. Unsupervised clustering analysis was performed to identify distinct patterns of liver involvement.</p><p><strong>Results: </strong>Liver involvement was identified in 71 patients (35%) and was independently associated with digestive and renal amyloidosis, liver uptake and increased vena cava diameter. Clustering analysis identified three phenotypes: a cardiac cluster, characterized by severe cardiac failure and congestive hepatopathy associated with elevated bilirubin; a hepatic cluster, marked by multivisceral amyloidosis, elevated γGT and ALP, in which liver involvement reflected amyloid deposition; an intermediate cluster with milder abnormalities and better prognosis. Histological findings supported this. Sixty-month survival was 32%, 44% and 54% in the cardiac, hepatic and intermediate clusters, respectively.</p><p><strong>Conclusion: </strong>Liver involvement in AL amyloidosis is due to both amyloid deposition and cardiac congestion. Clustering analysis revealed distinct liver patterns with different prognoses.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-17"},"PeriodicalIF":5.1,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148399943","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":"Proteostasis is disrupted in human endothelial cells by serum from ATTR patients and is rescued by tafamidis treatment.","authors":"Despoina D Gianniou, Dimitrios Delialis, Georgios Georgiopoulos, Dimitrios Bampatsias, Eirini Gkogkou, Foteini Theodorakakou, Panagiota Efstathia Nikolaou, Angeliki Choustoulaki, Alexandros Briasoulis, Ioannis Petropoulos, Eleni-Dimitra Papanagnou, Anna Dimoula, Julie Courraud, Raphael Patras, Angelos Soranidis, Meletios-Athanasios Dimopoulos, Ioannis P Trougakos, Efstathios Kastritis, Kimon Stamatelopoulos","doi":"10.1080/13506129.2026.2689643","DOIUrl":"https://doi.org/10.1080/13506129.2026.2689643","url":null,"abstract":"<p><strong>Background: </strong>The vascular effects of wild-type (ATTRwt-CM) and hereditary (ATTRv-CM) transthyretin cardiac amyloidosis, and the impact of tafamidis treatment, remain unclear.</p><p><strong>Methods: </strong>Serum from ATTRwt-CM and ATTRv-CM patients (pre- and 6-months post-Tafamidis treatment) elderly and young controls, was applied on human umbilical vein endothelial cells (HUVECs). Viability, motility, and stress responses and serum cytokine and proteomic profiles were assessed. Recombinant TTR, with and without tafamidis co-treatment, were also evaluated. Pulse wave velocity (PWV) was longitudinally assessed in ATTRwt-CM patients pre- and post-tafamidis treatment and in elderly controls.</p><p><strong>Results: </strong>ATTRwt-CM or ATTRv serum reduced HUVECs viability and motility, inducing proteotoxic and oxidative stress, while serum cytokine and proteome profiling revealed inflammatory-related signatures; All these effects were attenuated in HUVECs treated with post-Tafamidis serum. Recombinant TTR also induced proteotoxic stress, which was attenuated by tafamidis co-treatment (safety range ≤ 16 μM). Consistently, PWV was reduced in ATTRwt-CM patients after Tafamidis, as compared to controls, correlating with increased serum transthyretin and reduced PBMCs' proteasome activity.</p><p><strong>Conclusions: </strong>Serum from ATTR-CM patients or recombinant TTR directly induced toxic effects in HUVECs. Tafamidis mitigated these effects <i>in vitro</i> and improved arterial stiffness in ATTRwt-CM patients, implying protective vascular effects of tafamidis in ATTR-CM beyond direct myocardial transthyretin stabilization.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-15"},"PeriodicalIF":5.1,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334173","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":"Fluorine-18 florbetapir positron emission tomography unmasks amyloidosis with equivocal technetium-99m pyrophosphate findings driven by a novel transthyretin variant.","authors":"Xinglin Yang, Xuezhu Wang, Yuke Zhang, Xuemei Wang, Suxia Wang, Li Huo, Zhuang Tian","doi":"10.1080/13506129.2026.2676849","DOIUrl":"https://doi.org/10.1080/13506129.2026.2676849","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-5"},"PeriodicalIF":7.4,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229163","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}