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Here we revealed that A\u03b2 activates microglia and promotes the release of Galectin\u20109 (Gal\u20109), a member of the \u03b2\u2010galactoside\u2013binding family of lectins. The levels of Gal\u20109 in the cerebrospinal fluid and brain tissues of AD patients are higher than those in control subjects. Gal\u20109 interacts with A\u03b2 and promotes its aggregation, generating Gal\u20109\u2010A\u03b2 fibrils with enhanced seeding activity and neurotoxicity. The expression of Gal\u20109 increases with age in the brains of APP\/PS1 transgenic mice. Knockout of Gal\u20109 in APP\/PS1 mice substantially reduced A\u03b2 sedimentation, neuroinflammation, and cognitive impairment. Moreover, depletion of Gal\u20109 inhibited the seeding activity of brain homogenates from APP\/PS1 mice. These findings reveal a mechanism by which microglia\u2010derived Gal\u20109 accelerates A\u03b2 aggregation and seeding in AD. Thus, strategies aimed at inhibiting Gal\u20109 may hold promise as a disease\u2010modifying therapy to alleviate AD pathology.<\/jats:p>","DOI":"10.1111\/acel.14396","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T16:39:17Z","timestamp":1730479157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Microglia\u2010derived Galectin\u20109 drives amyloid\u2010\u03b2 pathology in Alzheimer's disease"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-3896","authenticated-orcid":false,"given":"Guoxin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyu","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan 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