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The AD-related pathology has been reported in several non-human animals, and most animals develop only the A\u03b2 or tau pathology. We herein describe the A\u03b2 and hp-tau pathology in the brains of aged pinniped species (seal, sea lion, and walrus). Molecular analyses revealed that the sequence of pinniped A\u03b2 was identical to that of human A\u03b2. Histopathological examinations detected argyrophilic plaques composed of A\u03b2 associated with dystrophic neurites in the cerebral cortex of aged pinnipeds. Astrogliosis and microglial infiltration were identified around A\u03b2 plaques. A\u03b2 deposits were observed in the blood vessel walls of the meninges and cerebrum. Pinniped tau protein was physiologically subjected to alternative splicing at exons 2, 3, and 10, and presented as five isoforms: two 3-repeat tau isoforms (1N3R, 2N3R) and three 4-repeat tau isoforms (0N4R, 1N4R, 2N4R); 0N3R tau isoform was absent. Histopathological examinations revealed argyrophilic fibrillar aggregates composed of hp-tau in the neuronal somata and neurites of aged pinniped brains. Few hp-tau aggregates were found in oligodendrocytes and microglia. Biochemically, hp-tau of the 3-repeat and 4-repeat isoforms was detected in brain sarkosyl-insoluble fractions. A\u03b2 and hp-tau both predominantly accumulated in the neocortex, particularly the frontal cortex. Furthermore, the activation of GSK-3\u03b2 was detected within cells containing hp-tau aggregates, and activated GSK-3\u03b2 was strongly expressed in cases with severe hp-tau pathologies. The present results suggest that, in association with A\u03b2 deposition, the activation of GSK-3\u03b2 contributes to hp-tau accumulation in pinniped brains. Here, we report that pinniped species naturally accumulate A\u03b2 and tau with aging, similar to the human AD pathology.<\/jats:p>","DOI":"10.1186\/s40478-020-01104-3","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T15:05:28Z","timestamp":1610031928000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Amyloid \u03b2 and tau pathology in brains of aged pinniped species (sea lion, seal, and walrus)"],"prefix":"10.1186","volume":"9","author":[{"given":"Yuta","family":"Takaichi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5273-7221","authenticated-orcid":false,"given":"James K.","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Soeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riki","family":"Koike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuko","family":"Katsumata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Kita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Haritani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Takashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"issue":"1","key":"1104_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3174\/ajnr.A0781","volume":"29","author":"FJ Wippold 2nd","year":"2008","unstructured":"Wippold FJ 2nd, Cairns N, Vo K, Holtzman DM, Morris JC (2008) Neuropathology for the neuroradiologist: plaques and tangles. 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