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Here, we conditionally deleted one allele of <jats:italic>myd88<\/jats:italic> gene specifically in microglia in APP\/PS1\u2010transgenic mice by 6\u2009months and analyzed AD\u2010associated pathologies by 9 months. We observed that heterozygous deletion of <jats:italic>myd88<\/jats:italic> gene in microglia decreased cerebral amyloid \u03b2 (A\u03b2) load and improved cognitive function of AD mice, which was correlated with reduced number of microglia in the brain and inhibited transcription of inflammatory genes, for example, <jats:italic>tnf\u2010\u03b1<\/jats:italic> and <jats:italic>il\u20101\u03b2<\/jats:italic>, in both brain tissues and individual microglia. To investigate mechanisms underlying the pathological improvement, we observed that haploinsufficiency of MyD88 increased microglial recruitment toward A\u03b2 deposits, which might facilitate A\u03b2 clearance. Microglia with haploinsufficient expression of MyD88 also increased vasculature in the brain of APP\/PS1\u2010transgenic mice, which was associated with up\u2010regulated transcription of <jats:italic>osteopontin<\/jats:italic> and <jats:italic>insulin\u2010like growth factor<\/jats:italic> genes in microglia. Moreover, MyD88\u2010haploinsufficient microglia elevated protein levels of LRP1 in cerebral capillaries of APP\/PS1\u2010transgenic mice. Cell culture experiments further showed that treatments with interleukin\u20101\u03b2 decreased LRP1 expression in pericytes. In summary, haploinsufficiency of MyD88 in microglia at a late disease stage attenuates pro\u2010inflammatory activation and amyloid pathology, prevents the impairment of microvasculature and perhaps also protects LRP1\u2010mediated A\u03b2 clearance in the brain of APP\/PS1\u2010transgenic mice, all of which improves neuronal function of AD mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/glia.24007","type":"journal-article","created":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T08:16:29Z","timestamp":1619943389000},"page":"1987-2005","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Haploinsufficiency of microglial <scp>MyD88<\/scp> ameliorates Alzheimer's pathology and vascular disorders in <scp>APP<\/scp>\/<scp>PS1<\/scp>\u2010transgenic mice"],"prefix":"10.1002","volume":"69","author":[{"given":"Wenqiang","family":"Quan","sequence":"first","affiliation":[{"name":"Department of Neurology Saarland University  Homburg Germany"},{"name":"German Institute for Dementia Prevention (DIDP) Saarland University  Homburg Germany"},{"name":"Department of Clinical Laboratory Tongji Hospital, Tongji University Medical School  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology Saarland University  Homburg Germany"},{"name":"German Institute for Dementia Prevention (DIDP) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlin","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurology Saarland University  Homburg Germany"},{"name":"German Institute for Dementia Prevention (DIDP) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Tomic","sequence":"additional","affiliation":[{"name":"Department of Neurology Saarland University  Homburg Germany"},{"name":"German Institute for Dementia Prevention (DIDP) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Furihata","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy Tokyo University of Pharmacy and Life Sciences  Hachioji Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Schulz\u2010Sch\u00e4ffer","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Menger","sequence":"additional","affiliation":[{"name":"Department of Experimental Surgery Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-868X","authenticated-orcid":false,"given":"Klaus","family":"Fassbender","sequence":"additional","affiliation":[{"name":"Department of Neurology Saarland University  Homburg Germany"},{"name":"German Institute for Dementia Prevention (DIDP) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-4233","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Saarland University  Homburg Germany"},{"name":"German Institute for Dementia Prevention (DIDP) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710329115"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4814-07.2008"},{"key":"e_1_2_9_4_1","first-page":"e53208","article-title":"Purification of mouse brain vessels","volume":"105","author":"Boulay A. 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