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Publications (10 of 127) Show all publications
Westermark, G., Nyström, E., Nyström, S., Nilsson, K. P., Hammarström, P. & Westermark, P. (2025). The question of strains in AA amyloidosis. Scientific Reports, 15(1), Article ID 3684.
Open this publication in new window or tab >>The question of strains in AA amyloidosis
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2025 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 15, no 1, article id 3684Article in journal (Refereed) Published
Abstract [en]

The existence of transmissible amyloid fibril strains has long intrigued the scientific community. The strain theory originates from prion disorders, but here, we provide evidence of strains in systemic amyloidosis. Human AA amyloidosis manifests as two distinct clinical phenotypes called common AA and vascular AA. Glomerular amyloid deposition of the kidney defines the common form, while in the vascular type amyloid deposits are massive in the renal medulla and in arteries throughout the body, while glomeruli are spared. By electron microscopy the two types appeared morphologically different. The common type was composed of dispersed fibrils which tended to be clustered whereas the vascular type was composed of longer and more distinct less clustered fibrils. Staining with fluorescent amyloid binding ligands analyzed by hyperspectral microscopy showed differential staining patterns between the two groups supporting the notion of human AA amyloid strains. AA amyloid staining was significantly different from systemic AL amyloid. Both types of AA (common and vascular) and AL amyloid fibrils were isolated and used to seed mouse AA amyloid in groups of inflamed NMRI mice (n = 9-10 per group). All but two mice showed amyloid deposits in the spleen induced by the human seeds. Amyloid binding ligand analysis was applied on the splenic amyloid deposits and revealed no clear significant difference between mice seeded with AA fibrils from different donors being vascular or common, but the AA deposits of mice given AL fibrils showed significantly different amyloid fluorescent signals compared to all groups of mice receiving AA fibrils. The combined results support the hypothesis that AA amyloid fibril structures can vary depending on the seed and may manifest as amyloid strains.

Place, publisher, year, edition, pages
Springer Nature, 2025
Keywords
Fluorescent amyloid ligands, Amyloid transmission, Prion, Protein aggregation, Amyloid strains
National Category
Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-550397 (URN)10.1038/s41598-025-87239-6 (DOI)001410922100050 ()39881136 (PubMedID)2-s2.0-85217357684 (Scopus ID)
Funder
Uppsala UniversitySwedish Research Council, 2023-03931
Available from: 2025-02-20 Created: 2025-02-20 Last updated: 2025-02-20Bibliographically approved
Buxbaum, J. N., Eisenberg, D. S., Fändrich, M., McPhail, E. D., Merlini, G., Saraiva, M. J. M., . . . Westermark, P. (2024). Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee. Amyloid: Journal of Protein Folding Disorders, 31(4), 249-256
Open this publication in new window or tab >>Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee
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2024 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 31, no 4, p. 249-256Article in journal (Refereed) Published
Abstract [en]

The ISA Nomenclature Committee met at the XIX International Symposium of Amyloidosis in Rochester, MN, 27 May 2024. The in-person event was followed by many electronic discussions, resulting in the current updated recommendations. The general nomenclature principles are unchanged. The total number of human amyloid fibril proteins is now 42 of which 19 are associated with systemic deposition, while 4 occur with either localised or systemic deposits. Most systemic amyloidoses are caused by the presence of protein variants which promote misfolding. However, in the cases of AA and ATTR the deposits most commonly consist of wild-type proteins and/or their fragments. One peptide drug, previously reported to create local iatrogenic amyloid deposits at its injection site, has been shown to induce rare instances of systemic deposition. The number of described animal amyloid fibril proteins is now 16, 2 of which are unknown in humans. Recognition of the importance of intracellular protein aggregates, which may have amyloid or amyloid-like properties, in many neurodegenerative diseases is rapidly increasing and their significance is discussed.

Place, publisher, year, edition, pages
Taylor & Francis, 2024
Keywords
Fibril, amyloid protein, nomenclature, intracellular aggregate, functional amyloid, iatrogenic amyloid
National Category
Biochemistry Molecular Biology Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-548052 (URN)10.1080/13506129.2024.2405948 (DOI)001326637700001 ()39350582 (PubMedID)2-s2.0-85205583967 (Scopus ID)
Available from: 2025-01-21 Created: 2025-01-21 Last updated: 2025-02-20Bibliographically approved
Schönland, S. & Westermark, P. (2024). Changes in the amyloid editorial board members and in editor positions. Amyloid: Journal of Protein Folding Disorders, 31(2), 85-85
Open this publication in new window or tab >>Changes in the amyloid editorial board members and in editor positions
2024 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 31, no 2, p. 85-85Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2024
National Category
Biochemistry Molecular Biology
Identifiers
urn:nbn:se:uu:diva-532641 (URN)10.1080/13506129.2024.2344167 (DOI)001230857100013 ()38781088 (PubMedID)
Available from: 2024-06-20 Created: 2024-06-20 Last updated: 2025-02-20Bibliographically approved
Westermark, P. & Merlini, G. (2024). Successes in translation. Amyloid: Journal of Protein Folding Disorders, 31(3), 159-167
Open this publication in new window or tab >>Successes in translation
2024 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 31, no 3, p. 159-167Article, review/survey (Refereed) Published
Abstract [en]

Translational research is key in advancing the diagnosis and therapy of systemic amyloidoses. This paper summarises our presentations at the ISA Workshop on Translation in Systemic Amyloidoses held in Athens on September 25-26, 2023. The critical advances made by the pioneers in the field are reviewed, with particular attention to the discoveries and developments of utmost importance to our understanding of what amyloid is and how the substance affects functions. Examples of translational research regarding the mechanisms of cardiac damage in light chain amyloidosis, the role of biomarkers in improving our understanding of the biology of the disease and patients' management, and the molecular mechanisms involved in the cytotoxicity are described. Advances in basic research continue to open new therapeutic avenues.

Place, publisher, year, edition, pages
Taylor & Francis, 2024
Keywords
Amyloidosis, history, translation, pathogenesis
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-549111 (URN)10.1080/13506129.2024.2387163 (DOI)001284069700001 ()39101820 (PubMedID)
Available from: 2025-02-06 Created: 2025-02-06 Last updated: 2025-02-06Bibliographically approved
Sonavane, S., Westermark, P., Rising, A. & Holm, L. (2023). Regionalization of cell types in silk glands of Larinioides sclopetarius suggest that spider silk fibers are complex layered structures. Scientific Reports, 13, Article ID 22273.
Open this publication in new window or tab >>Regionalization of cell types in silk glands of Larinioides sclopetarius suggest that spider silk fibers are complex layered structures
2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, article id 22273Article in journal (Refereed) Published
Abstract [en]

In order to produce artificial silk fibers with properties that match the native spider silk we likely need to closely mimic the spinning process as well as fiber architecture and composition. To increase our understanding of the structure and function of the different silk glands of the orb weaver Larinioides sclopetarius, we used resin sections for detailed morphology, paraffin embedded sections for a variety of different histological stainings, and a histochemical method for localization of carbonic anhydrase activity. Our results show that all silk glands, except the tubuliform glands, are composed of two or more columnar epithelial cell types, some of which have not been described previously. We observed distinct regionalization of the cell types indicating sequential addition of secretory products during silk formation. This means that the major ampullate, minor ampullate, aciniform type II, and piriform silk fibers most likely are layered and that each layer has a specific composition. Furthermore, a substance that stains positive for polysaccharides may be added to the silk in all glands except in the type I aciniform glands. Active carbonic anhydrase was found in all silk glands and/or ducts except in the type I aciniform and tubuliform glands, with the strongest staining in aggregate glands and their ductal nodules. Carbonic anhydrase plays an important role in the generation of a pH gradient in the major ampullate glands, and our results suggest that some other glands may also harbor pH gradients.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Biochemistry Molecular Biology
Identifiers
urn:nbn:se:uu:diva-524297 (URN)10.1038/s41598-023-49587-z (DOI)001125340600062 ()38097700 (PubMedID)
Funder
EU, European Research Council, 815357Olle Engkvists stiftelse, 207-0375Swedish Research Council Formas, 2019-00427
Available from: 2024-03-04 Created: 2024-03-04 Last updated: 2025-02-20Bibliographically approved
Pistis, K. D., Westermark, P., Qureshi, A. R., Beshara, S., Sterner, G., Barany, P. & Linde, T. (2023). The effect of high-dose vitamin D supplementation on hepcidin-25 and erythropoiesis in patients with chronic kidney disease. BMC Nephrology, 24(1), Article ID 20.
Open this publication in new window or tab >>The effect of high-dose vitamin D supplementation on hepcidin-25 and erythropoiesis in patients with chronic kidney disease
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2023 (English)In: BMC Nephrology, E-ISSN 1471-2369, Vol. 24, no 1, article id 20Article in journal (Refereed) Published
Abstract [en]

Background: Hepcidin is considered to play a central role in the pathophysiology of renal anemia. Recent studies in healthy individuals have demonstrated a suppressive effect of vitamin D (VD) on the expression of hepcidin. In this post-hoc analysis based on a randomized controlled study, we evaluated the effect of supplementing chronic kidney disease (CKD) patients (stage G3-G4) with a high daily dose of native VD on serum levels of hepcidin-25, the hepcidin/ferritin ratio, as well as on markers of erythropoiesis.

Methods: Patients with CKD stage G3-G4 included in a double blind, randomized, placebo (PBO) controlled study with available hepcidin measurements were analyzed. Study subjects received either 8000 international units (IU) of cholecalciferol daily or PBO for 12 weeks. We evaluated the change in markers of hepcidin expression, erythropoiesis, and iron status from baseline to week 12 and compared the change between the groups.

Results: Eighty five patients completed the study. Calcitriol, but not 25-hydroxyvitamin D (25(OH) D), was inversely correlated with serum levels of hepcidin-25 (rho = -0,38; p = < 0, 01 and rho = -0,02; p = 0, 89, respectively) at baseline. Supplementation with VD significantly raised the serum concentration of serum 25(OH)D in the treatment group (from 54 (39-71) to 156 (120-190) nmol/L; p = < 0, 01)) but had no effect on any of the markers of hepcidin, erythropoiesis, or iron status in the entire cohort. However, we did observe an increase in hemoglobin (HB) levels and transferrin saturation (TSAT) as compared to the PBO group in a subgroup of patients with low baseline 25(OH)D levels (< 56 nmol/L). In contrast, in patients with high baseline 25(OH)D values (>= 56 nmol/L), VD supplementation associated with a decrease in HB levels and TSAT (p = 0,056) within the VD group in addition to a decrease in hepcidin levels as compared to the PBO group.

Conclusion: High-dose VD supplementation had no discernible effect on markers of hepcidin or erythropoiesis in the entire study cohort. However, in patients with low baseline 25(OH)D levels, high-dose VD supplementation associated with beneficial effects on erythropoiesis and iron availability. In contrast, in patients with elevated baseline 25(OH)D levels, high-dose VD supplementation resulted in a decrease in hepcidin levels, most likely due to a deterioration in iron status.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Chronic kidney disease, Anemia, Vitamin D, Iron, Hepcidin
National Category
Hematology Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-497774 (URN)10.1186/s12882-022-03014-z (DOI)000918024500001 ()36698076 (PubMedID)
Available from: 2023-03-08 Created: 2023-03-08 Last updated: 2025-02-18Bibliographically approved
Buxbaum, J. N., Dispenzieri, A., Eisenberg, D. S., Fändrich, M., Merlini, G., Saraiva, M. J. M., . . . Westermark, P. (2022). Amyloid nomenclature 2022: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee. Amyloid: Journal of Protein Folding Disorders, 29(4), 213-219
Open this publication in new window or tab >>Amyloid nomenclature 2022: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee
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2022 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 29, no 4, p. 213-219Article in journal (Refereed) Published
Abstract [en]

The Nomenclature Committee of the International Society of Amyloidosis met at the XVIII International Symposium on Amyloidosis in September and virtually in October 2022 with discussions resulting in this upgraded nomenclature recommendation. The nomenclature principles remain unchanged but there is an ongoing discussion regarding the importance and varying nature of intracellular protein aggregates, particularly those associated with neurodegenerative diseases. Six novel proteins were added to the list of human amyloid fibril proteins. Of these, three are polypeptide hormones and two currently utilised peptide drugs, making the number of known iatrogenic amyloid forms four, all appearing as subcutaneous nodules at the injection site. The sixth novel amyloid fibril protein is the transmembrane 106B protein, forming intracellular amyloid fibrils in disorders associated with frontotemporal dementia. The number of known human amyloid fibril proteins is now 42.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2022
Keywords
Fibril, amyloid protein, nomenclature, intracellular aggregate, functional
National Category
Biochemistry Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-497012 (URN)10.1080/13506129.2022.2147636 (DOI)000890933200001 ()36420821 (PubMedID)
Available from: 2023-02-23 Created: 2023-02-23 Last updated: 2025-02-20Bibliographically approved
Benson, M. D., Berk, J. L., Dispenzieri, A., Damy, T., Gillmore, J. D., Hazenberg, B. P., . . . Westermark, P. (2022). Tissue biopsy for the diagnosis of amyloidosis: experience from some centres. Amyloid: Journal of Protein Folding Disorders, 29(1), 8-13
Open this publication in new window or tab >>Tissue biopsy for the diagnosis of amyloidosis: experience from some centres
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2022 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 29, no 1, p. 8-13Article in journal (Refereed) Published
Abstract [en]

A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.

Place, publisher, year, edition, pages
Taylor & FrancisInforma UK Limited, 2022
Keywords
Amyloid, method, immunohistochemistry, mass spectrometry
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-479423 (URN)10.1080/13506129.2021.1994386 (DOI)000717867500001 ()34766859 (PubMedID)
Available from: 2022-06-30 Created: 2022-06-30 Last updated: 2024-12-03Bibliographically approved
Vesterlund Damjanovic, J., Ihse, E., Thelander, U., Zancanaro, A., Westermark, G. & Westermark, P. (2022). Tissue-based diagnosis of systemic amyloidosis: Experience of the informal diagnostic center at Uppsala University Hospital. Upsala Journal of Medical Sciences, 127(1), Article ID e8913.
Open this publication in new window or tab >>Tissue-based diagnosis of systemic amyloidosis: Experience of the informal diagnostic center at Uppsala University Hospital
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2022 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 127, no 1, article id e8913Article in journal (Refereed) Published
Abstract [en]

Diagnosis of systemic amyloidosis is a clinical challenge and usually relies on a tissue biopsy. We have developed diagnostic methods based on the presence of amyloid deposits in abdominal subcutaneous fat tissue. This tissue is also used to determine the biochemical type of amyloidosis, performed by western blot and immunohistochemical analyses with the aid of in-house developed rabbit antisera and mouse monoclonal antibodies. Mass spectrometric methods are under development for selected cases. The diagnostic outcome for 2018-2020 was studied. During this period, we obtained 1,562 biopsies, of which 1,397 were unfixed subcutaneous fat tissue with varying degrees of suspicion of systemic amyloidosis. Of these, 440 contained amyloid deposits. The biochemical nature of the amyloid was determined by western blot analysis in 319 specimens and by immunohistochemistry in further 51 cases.

Place, publisher, year, edition, pages
Upsala Medical SocietyUPSALA MED SOC, 2022
Keywords
Amyloidosis, systemic, monoclonal antibodies, subcutaneous fat tissue, biopsy
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-489379 (URN)10.48101/ujms.v127.8913 (DOI)000879745200001 ()36337276 (PubMedID)
Available from: 2023-01-02 Created: 2023-01-02 Last updated: 2024-12-03Bibliographically approved
Rising, A., Gherardi, P., Chen, G., Johansson, J., Oskarsson, M. E., Westermark, G. & Westermark, P. (2021). AA amyloid in human food chain is a possible biohazard. Scientific Reports, 11(1), Article ID 21069.
Open this publication in new window or tab >>AA amyloid in human food chain is a possible biohazard
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2021 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 21069Article in journal (Refereed) Published
Abstract [en]

AA amyloidosis can be transmitted experimentally in several mammalian and avian species as well as spontaneously between captive animals, even by oral intake of amyloid seeds. Amyloid seeding can cross species boundaries, and fibrils of one kind of amyloid protein may also seed other types. Here we show that meat from Swedish and Italian cattle for consumption by humans often contains AA amyloid and that bovine AA fibrils efficiently cross-seed human amyloid beta peptide, associated with Alzheimer's disease.

Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2021
National Category
Biochemistry Molecular Biology
Identifiers
urn:nbn:se:uu:diva-459015 (URN)10.1038/s41598-021-00588-w (DOI)000711622600096 ()34702933 (PubMedID)
Available from: 2021-11-23 Created: 2021-11-23 Last updated: 2025-02-20Bibliographically approved
Projects
The systemic amyloidoses and their relationship to prion disorders [2008-07418_VR]; Uppsala UniversityNature, pathogenesis and impact of different forms of amyloid [2009-02877_VR]; Uppsala University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2756-4995

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