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However, where and how circulating A\u03b2 is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of A\u03b2 in the periphery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the physiological clearance of A\u03b2 by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP\/PS1\u00a0mice to investigate the effect of splenectomy on AD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that A\u03b2 levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating A\u03b2 is cleared when blood flows through the spleen. Next, we found that splenic monocytes\/macrophages could take up A\u03b2 directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain A\u03b2 burden and AD\u2010related pathologies in AD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating A\u03b2 in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acel.13533","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T21:44:37Z","timestamp":1640295877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Physiological clearance of A\u03b2 by spleen and splenectomy aggravates Alzheimer\u2010type pathogenesis"],"prefix":"10.1111","volume":"21","author":[{"given":"Zhong\u2010Yuan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience Daping Hospital Third Military Medical University  Chongqing China"},{"name":"Institute of Brain and Intelligence Third Military Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Ageing and Brain Diseases  Chongqing 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