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Despite its unique pathology, the pathogenic mechanisms of this disease are only partially understood. This is in part because comparative pathological studies on fibrinogen A\u03b1\u2010chain amyloidosis are currently unavailable as there is a lack of reported cases in animals other than humans. In this study, mass spectrometry\u2010based proteomic analyses of Japanese squirrels (<jats:italic>Sciurus lis<\/jats:italic>) that died in five Japanese zoos showed that they developed glomerular\u2010associated fibrinogen A\u03b1\u2010chain amyloidosis with an extremely high incidence rate (29\/38 cases, 76.3%). The condition was found to be age\u2010dependent in the Japanese squirrels, with 89% of individuals over 4\u2009years of age affected. Mass spectrometry revealed that the C\u2010terminal region of the fibrinogen A\u03b1\u2010chain was involved in amyloidogenesis in Japanese squirrels as well as humans. No gene variations were identified between amyloid\u2010positive and amyloid\u2010negative squirrels, which contrasted with the available data for humans. The results indicate that fibrinogen A\u03b1\u2010chain amyloidosis is a senile amyloidosis in Japanese squirrels. The results have also provided comparative pathological support that the amyloidogenic C\u2010terminal region of the fibrinogen A\u03b1\u2010chain is involved in the characteristic glomerular pathology, regardless of the animal species. This study elucidates the potential causes of death in Japanese squirrels and will contribute to future comparative pathological studies of fibrinogen A\u03b1\u2010chain amyloidosis. \u00a9 2023 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6150","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T23:31:13Z","timestamp":1691451073000},"page":"96-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Fibrinogen A\u03b1\u2010chain amyloidosis outbreaks in Japanese squirrels (<scp><i>Sciurus lis<\/i><\/scp>): a potential disease model"],"prefix":"10.1002","volume":"261","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0601-9137","authenticated-orcid":false,"given":"Susumu","family":"Iwaide","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Toxicology Tokyo University of Agriculture and Technology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanami","family":"Ito","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology Nihon University  Fujisawa\u2010shi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Ogino","sequence":"additional","affiliation":[{"name":"Cooperative Department of Veterinary Medicine Iwate University  Morioka\u2010shi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsumi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Toxicology Tokyo University of Agriculture and Technology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Koyama","sequence":"additional","affiliation":[{"name":"Laboratory of Ethology, Tokyo University of Agriculture and Technology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7855-7621","authenticated-orcid":false,"given":"Shumpei","family":"Hisamoto","sequence":"additional","affiliation":[{"name":"Meiji Institute for Advanced Study of Mathematical Sciences  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-0417","authenticated-orcid":false,"given":"Hirotaka","family":"Kondo","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology Nihon University  Fujisawa\u2010shi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1905-1783","authenticated-orcid":false,"given":"Yoshiyuki","family":"Itoh","sequence":"additional","affiliation":[{"name":"Smart\u2010Core\u2010Facility Promotion Organization, Tokyo University of Agriculture and Technology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Hisada","sequence":"additional","affiliation":[{"name":"Smart\u2010Core\u2010Facility Promotion Organization, Tokyo University of Agriculture and Technology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Cooperative Department of Veterinary Medicine Iwate University  Morioka\u2010shi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Kyoto City Zoo, Sakyo\u2010ku  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Morioka Zoological Park  Morioka\u2010shi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-3196","authenticated-orcid":false,"given":"Shin\u2010ichi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Okayama University of Science  Imabari\u2010shi Japan"},{"name":"Kyoto Institute of Nutrition &amp; Pathology Inc.  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