Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats
Abstract The kidneys are one of the primary organs affected by amyloid A (AA) amyloidosis in mixed-breed cats. The distribution of amyloid deposits within the kidneys varies among individuals; however, the underlying cause is unknown. This study investigated the association between serum AA (SAA) po...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-07983-7 |
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| author | Natsumi Kobayashi Masahiro Kaneda Mitsuhiro Ikeda Hirotaka Kondo Susumu Iwaide Yoshiyuki Itoh Miki Hisada Yuka Kato Niki Sedghi Masoud Kohji Nomura Machie Tsuneyasu Tomoko Akamine Tomoaki Murakami |
| author_facet | Natsumi Kobayashi Masahiro Kaneda Mitsuhiro Ikeda Hirotaka Kondo Susumu Iwaide Yoshiyuki Itoh Miki Hisada Yuka Kato Niki Sedghi Masoud Kohji Nomura Machie Tsuneyasu Tomoko Akamine Tomoaki Murakami |
| author_sort | Natsumi Kobayashi |
| collection | DOAJ |
| description | Abstract The kidneys are one of the primary organs affected by amyloid A (AA) amyloidosis in mixed-breed cats. The distribution of amyloid deposits within the kidneys varies among individuals; however, the underlying cause is unknown. This study investigated the association between serum AA (SAA) polymorphisms and the pattern of renal amyloid deposition in five mixed-breed cats. Histological analysis of the kidneys revealed amyloid deposits in the renal glomeruli and renal papillae in all cases. In contrast, the amyloid deposition pattern differed in the medulla, with widespread deposition from the corticomedullary junctional area to the inner medulla in two of the five cats. These amyloids were mainly located in the basement membrane of the renal tubules, extending towards the lumen and into the interstitium. Conversely, in the other three cats, amyloid deposition in the medulla was sparse and the deposits were localized in the perivascular stroma in the corticomedullary junction. Genetic analysis identified four SAA alleles involving six amino acid substitutions (Q1E, I29K, D42E, Q45R, P48R, and A51V). Mass spectrometry and immunohistochemistry revealed that AA amyloid derived from SAA with Q45 was predominantly deposited in the cortex and papilla, as well as in the perivascular stroma of some parts of the outer medulla. On the other hand, AA amyloid derived from SAA with R45 was specifically observed around the tubules in the renal inner to outer medulla. Except for Q45R, no substitutions were associated with distribution patterns. These findings suggest that the SAA polymorphism sequence is associated with the site of AA amyloid deposition in the kidney. Moreover, this study is the first report of such a complex pattern of amyloid deposition in the organ of the same individual, emphasizing that the primary structure of the amyloid precursor protein determines amyloid distribution. |
| format | Article |
| id | doaj-art-c8e7af12b98f48478cf05bb420af1192 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-c8e7af12b98f48478cf05bb420af11922025-08-20T03:45:19ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-07983-7Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in catsNatsumi Kobayashi0Masahiro Kaneda1Mitsuhiro Ikeda2Hirotaka Kondo3Susumu Iwaide4Yoshiyuki Itoh5Miki Hisada6Yuka Kato7Niki Sedghi Masoud8Kohji Nomura9Machie Tsuneyasu10Tomoko Akamine11Tomoaki Murakami12Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Anatomy, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pathology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon UniversityLaboratory of Veterinary Pathology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon UniversityLaboratory of Veterinary Toxicology, Tokyo University of Agriculture and TechnologySmart-Core-Facility Promotion Organization, Tokyo University of Agriculture and TechnologySmart-Core-Facility Promotion Organization, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Toxicology, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Toxicology, Tokyo University of Agriculture and TechnologyVeterinary Diagnostic Pathology Section, MLT Co., LtdWatanabe Animal Hospital, Anicom Specialty Medical Institute IncWatanabe Animal Hospital, Anicom Specialty Medical Institute IncLaboratory of Veterinary Toxicology, Tokyo University of Agriculture and TechnologyAbstract The kidneys are one of the primary organs affected by amyloid A (AA) amyloidosis in mixed-breed cats. The distribution of amyloid deposits within the kidneys varies among individuals; however, the underlying cause is unknown. This study investigated the association between serum AA (SAA) polymorphisms and the pattern of renal amyloid deposition in five mixed-breed cats. Histological analysis of the kidneys revealed amyloid deposits in the renal glomeruli and renal papillae in all cases. In contrast, the amyloid deposition pattern differed in the medulla, with widespread deposition from the corticomedullary junctional area to the inner medulla in two of the five cats. These amyloids were mainly located in the basement membrane of the renal tubules, extending towards the lumen and into the interstitium. Conversely, in the other three cats, amyloid deposition in the medulla was sparse and the deposits were localized in the perivascular stroma in the corticomedullary junction. Genetic analysis identified four SAA alleles involving six amino acid substitutions (Q1E, I29K, D42E, Q45R, P48R, and A51V). Mass spectrometry and immunohistochemistry revealed that AA amyloid derived from SAA with Q45 was predominantly deposited in the cortex and papilla, as well as in the perivascular stroma of some parts of the outer medulla. On the other hand, AA amyloid derived from SAA with R45 was specifically observed around the tubules in the renal inner to outer medulla. Except for Q45R, no substitutions were associated with distribution patterns. These findings suggest that the SAA polymorphism sequence is associated with the site of AA amyloid deposition in the kidney. Moreover, this study is the first report of such a complex pattern of amyloid deposition in the organ of the same individual, emphasizing that the primary structure of the amyloid precursor protein determines amyloid distribution.https://doi.org/10.1038/s41598-025-07983-7AmyloidosisMass spectrometrySerum amyloid ARenal diseaseFelis catus |
| spellingShingle | Natsumi Kobayashi Masahiro Kaneda Mitsuhiro Ikeda Hirotaka Kondo Susumu Iwaide Yoshiyuki Itoh Miki Hisada Yuka Kato Niki Sedghi Masoud Kohji Nomura Machie Tsuneyasu Tomoko Akamine Tomoaki Murakami Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats Scientific Reports Amyloidosis Mass spectrometry Serum amyloid A Renal disease Felis catus |
| title | Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats |
| title_full | Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats |
| title_fullStr | Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats |
| title_full_unstemmed | Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats |
| title_short | Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats |
| title_sort | polymorphisms in saa alter intrarenal amyloid distribution of aa amyloidosis in cats |
| topic | Amyloidosis Mass spectrometry Serum amyloid A Renal disease Felis catus |
| url | https://doi.org/10.1038/s41598-025-07983-7 |
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