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Previous studies focused on microglial amyloid\u2010\u03b2 (A\u03b2) phagocytosis with less attention on the impact of TREM2\n R47H<\/jats:sup>\n mutation on blood monocytes.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Bone marrow transplantation (BMT) models were used to assess the contribution of blood monocytes carrying TREM2\n R47H<\/jats:sup>\n mutation to AD.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n A\u03b2 phagocytosis was compromised in mouse monocytes carrying the TREM2\n R47H<\/jats:sup>\n mutation. Transplantation of bone marrow cells (BMCs) carrying TREM2\n R47H<\/jats:sup>\n mutation increased cerebral A\u03b2 burden and aggravated AD\u2010type pathologies. Moreover, the replacement of TREM2\n R47H<\/jats:sup>\n \u2010BMCs restored monocytic A\u03b2 phagocytosis, lowered A\u03b2 levels in the blood and brain, and improved cognitive function.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n Our study reveals that blood monocytes carrying the TREM2\n R47H<\/jats:sup>\n mutation substantially contribute to the pathogenesis of AD, and correcting the TREM2\n R47H<\/jats:sup>\n mutation in BMCs would be a potential therapeutic approach for those carrying this mutation.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n \n TREM2\n R47H<\/jats:sup>\n mutation compromises the A\u03b2 phagocytosis of blood monocytes.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Blood monocytes carrying TREM2\n R47H<\/jats:sup>\n mutation contribute substantially to AD pathogenesis.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Correction of the TREM2\n R47H<\/jats:sup>\n mutation in bone marrow cells ameliorates AD pathologies and cognitive impairments.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.14402","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T01:10:54Z","timestamp":1735607454000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Roles of blood monocytes carrying TREM2\n R47H<\/sup>\n mutation in pathogenesis of Alzheimer's disease and its therapeutic potential in APP\/PS1 mice"],"prefix":"10.1002","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 Chongqing China"},{"name":"Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing 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Neurology and Centre for Clinical Neuroscience Daping Hospital, Third Military Medical University Chongqing China"},{"name":"Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Feng","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience Daping Hospital, Third Military Medical University Chongqing China"},{"name":"Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience Daping Hospital, Third Military Medical University Chongqing China"},{"name":"Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing 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Key Laboratory of Ageing and Brain Diseases Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience Daping Hospital, Third Military Medical University Chongqing China"},{"name":"Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Hua","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience Daping Hospital, Third Military Medical University Chongqing China"},{"name":"Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Yu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience Daping Hospital, Third Military Medical 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