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In this study, we aimed to clarify the mechanisms by which cerebral hypoperfusion may exacerbate AD pathology. We applied bilateral common carotid artery stenosis (BCAS) to a mice model of AD and evaluated how the equilibrium of amyloid \u03b2 oligomers respond to hypoperfusion. BCAS accelerated amyloid \u03b2 (A\u03b2) convergence to the aggregation seed, facilitating the growth of A\u03b2 plaques, but without changing the total A\u03b2 amount in the brain. Furthermore, A\u03b2 oligomers with high molecular weight increased in the brain of BCAS-operated mice. Considering A\u03b2 is in an equilibrium among monomeric, oligomeric, and aggregation forms, our data suggest that cerebral hypoperfusion after BCAS shifted this equilibrium to a state where a greater number of A\u03b2 molecules participate in A\u03b2 assemblies to form aggregation-prone A\u03b2 oligomers with high molecular weight. The reduced blood flow in the cerebral arteries due to BCAS attenuated the dynamics of the interstitial fluid leading to congestion, which may have facilitated A\u03b2 aggregation. We suggest that cerebral hypoperfusion may accelerate AD by enhancing the tendency of A\u03b2 to become aggregation-prone.<\/jats:p>","DOI":"10.1038\/s41598-019-39494-7","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T06:49:58Z","timestamp":1551163798000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Chronic cerebral hypoperfusion shifts the equilibrium of amyloid \u03b2 oligomers to aggregation-prone species with higher molecular weight"],"prefix":"10.1038","volume":"9","author":[{"given":"Taro","family":"Bannai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Mano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xigui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaku","family":"Ohtomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Ohtomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeyuki","family":"Tsuchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kagari","family":"Koshi-Mano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadafumi","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Okazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwatsubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5602-5686","authenticated-orcid":false,"given":"Shoji","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsushi","family":"Toda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,26]]},"reference":[{"key":"39494_CR1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy, J. & Selkoe, D. 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