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In this study, we discovered that the intrahippocampal injection of soluble amyloid-\u03b2 species with a molecular weight of &amp;gt;150\u2005kDa isolated from the brains of plaque-laden amyloid-\u03b2 precursor protein transgenic mice or patients with Alzheimer\u2019s disease using size-exclusion chromatography, dramatically accelerated \u03b2-amyloidosis in the transgenic mice brains. In contrast, intrahippocampal injection of soluble amyloid-\u03b2 species with 50\u201370\u2005kDa or 10\u201320\u2005kDa never induced \u03b2-amyloidosis. Moreover, injection of the soluble amyloid-\u03b2 species with &amp;gt;150\u2005kDa into cerebrospinal fluid of young transgenic mice via the cisterna magna predominantly induced amyloid-\u03b2 deposition within the wall of leptomeningeal arteries surrounding the brain, reminiscent of cerebral amyloid angiopathy. The seeding activity of the soluble high-molecular-weight amyloid-\u03b2 was prevented by the immunodepletion of amyloid-\u03b2 and abolished by formic acid denaturation, suggesting that these amyloid-\u03b2 oligomers are crucial in inducing \u03b2-amyloidosis. Furthermore, we have shown that the soluble high-molecular-weight amyloid-\u03b2 is present in the brains of patients with Alzheimer\u2019s disease and induced \u03b2-amyloidosis. These results indicate that the soluble high-molecular-weight amyloid-\u03b2 oligomers may play an important role in the spatiotemporal spreading of amyloid-\u03b2 deposition in Alzheimer\u2019s disease brains.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag188","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:22:06Z","timestamp":1779794526000},"source":"Crossref","is-referenced-by-count":0,"title":["Soluble high-molecular-weight amyloid-\u03b2 species derived from amyloid-\u03b2-laden brains induce cerebral \u03b2-amyloidosis"],"prefix":"10.1093","volume":"8","author":[{"given":"Mayu","family":"Kashiwagi-Hakozaki","sequence":"first","affiliation":[{"name":"Department of Neuropathology, Graduate School of Medicine, The University of Tokyo , Tokyo 113-0033 ,","place":["Japan"]},{"name":"Department of Pathology, Graduate School of Medicine, The University of Tokyo , Tokyo 113-0033 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