{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:48:53Z","timestamp":1791528533491,"version":"4.3.4"},"reference-count":89,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30-AG066519"],"award-info":[{"award-number":["P30-AG066519"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AG056303"],"award-info":[{"award-number":["R01-AG056303"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG061895"],"award-info":[{"award-number":["R01AG061895"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R61-HL154307"],"award-info":[{"award-number":["R61-HL154307"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1-AG055524"],"award-info":[{"award-number":["RF1-AG055524"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1-DA048813"],"award-info":[{"award-number":["RF1-DA048813"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32-AG00096"],"award-info":[{"award-number":["T32-AG00096"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32-AG073088"],"award-info":[{"award-number":["T32-AG073088"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1163981"],"award-info":[{"award-number":["GNT1163981"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["T32-NS082174"],"award-info":[{"award-number":["T32-NS082174"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","award":["EDUC4-12822"],"award-info":[{"award-number":["EDUC4-12822"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer's Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015471","name":"Mater Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015471","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2022,6]]},"DOI":"10.1016\/j.celrep.2022.110961","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T10:55:01Z","timestamp":1655204101000},"page":"110961","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":160,"title":["Absence of microglia promotes diverse pathologies and early lethality in Alzheimer\u2019s disease mice"],"prefix":"10.1016","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-116X","authenticated-orcid":false,"given":"Sepideh","family":"Kiani Shabestari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7768-4856","authenticated-orcid":false,"given":"Samuel","family":"Morabito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0737-9311","authenticated-orcid":false,"given":"Emma Pascal","family":"Danhash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5368-6788","authenticated-orcid":false,"given":"Amanda","family":"McQuade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Ramirez","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-0560","authenticated-orcid":false,"given":"Emily","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul","family":"Chadarevian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Claes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4888-1671","authenticated-orcid":false,"given":"Morgan Alexandra","family":"Coburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-9850","authenticated-orcid":false,"given":"Jonathan","family":"Hasselmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Hidalgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla Nhi","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8447-6756","authenticated-orcid":false,"given":"Alessandra C.","family":"Martini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-8124","authenticated-orcid":false,"given":"Winston","family":"Chang Rothermich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3307-0887","authenticated-orcid":false,"given":"Jesse","family":"Pascual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-6396","authenticated-orcid":false,"given":"Elizabeth","family":"Head","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2615-1478","authenticated-orcid":false,"given":"David A.","family":"Hume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9423-557X","authenticated-orcid":false,"given":"Clare","family":"Pridans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayk","family":"Davtyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3762-2746","authenticated-orcid":false,"given":"Vivek","family":"Swarup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-7157","authenticated-orcid":false,"given":"Mathew","family":"Blurton-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2022.110961_bib1","first-page":"4489","article-title":"Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking \u03b1V\u03b28-TGF\u03b2 signaling in the brain","volume":"141","author":"Arnold","year":"2014","journal-title":"Dev. Camb. Engl."},{"key":"10.1016\/j.celrep.2022.110961_bib2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/ana.22112","article-title":"Cerebral amyloid angiopathy pathology and cognitive domains in older persons","volume":"69","author":"Arvanitakis","year":"2011","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.celrep.2022.110961_bib3","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1001\/jamaneurol.2017.1062","article-title":"Brain calcifications in adult-onset genetic leukoencephalopathies: a review","volume":"74","author":"Ayrignac","year":"2017","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.celrep.2022.110961_bib4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00401-009-0522-3","article-title":"Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer\u2019s disease","volume":"118","author":"Bell","year":"2009","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.celrep.2022.110961_bib5","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1186\/s12974-018-1348-5","article-title":"Partial reduction of microglia does not affect tau pathology in aged mice","volume":"15","author":"Bennett","year":"2018","journal-title":"J.\u00a0Neuroinflammation"},{"key":"10.1016\/j.celrep.2022.110961_bib6","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.immuni.2015.06.012","article-title":"Genetic cell ablation reveals clusters of local self-renewing microglia in the mammalian central nervous system","volume":"43","author":"Bruttger","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2022.110961_bib7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1749-6632.2002.tb04801.x","article-title":"Molecular and functional dissection of TGF-\u03b21-induced cerebrovascular abnormalities in transgenic mice","volume":"977","author":"Buckwalter","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.celrep.2022.110961_bib8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.celrep.2022.110961_bib9","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.celrep.2022.110961_bib10","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/bs.ctdb.2016.10.004","article-title":"Regulation of embryonic and postnatal development by the CSF-1 receptor","volume":"123","author":"Chitu","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"10.1016\/j.celrep.2022.110961_bib11","doi-asserted-by":"crossref","first-page":"eabe4601","DOI":"10.1126\/sciadv.abe4601","article-title":"Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and \u03b2-amyloid pathology","volume":"7","author":"Da Mesquita","year":"2021","journal-title":"Sci. Adv."},{"key":"10.1016\/j.celrep.2022.110961_bib12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s12974-015-0366-9","article-title":"Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice","volume":"12","author":"Dagher","year":"2015","journal-title":"J.\u00a0Neuroinflammation"},{"key":"10.1016\/j.celrep.2022.110961_bib13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1182\/blood.V99.1.111","article-title":"Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects","volume":"99","author":"Dai","year":"2002","journal-title":"Blood"},{"key":"10.1016\/j.celrep.2022.110961_bib14","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.neurobiolaging.2003.12.026","article-title":"The microglial phagocytic role with specific plaque types in the Alzheimer disease brain","volume":"25","author":"D\u2019Andrea","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.celrep.2022.110961_bib15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.celrep.2022.110961_bib16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.celrep.2022.110961_bib17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13024-017-0184-x","article-title":"Late onset Alzheimer\u2019s disease genetics implicates microglial pathways in disease risk","volume":"12","author":"Efthymiou","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.celrep.2022.110961_bib18","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neuron.2014.02.040","article-title":"Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain","volume":"82","author":"Elmore","year":"2014","journal-title":"Neuron"},{"key":"10.1016\/j.celrep.2022.110961_bib19","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00401-002-0640-7","article-title":"Immunohistochemical examination on intracranial calcification in neurodegenerative diseases","volume":"105","author":"Fujita","year":"2003","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.celrep.2022.110961_bib20","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.4049\/jimmunol.2000835","article-title":"A transgenic line that reports CSF1R protein expression provides a definitive marker for the mouse mononuclear phagocyte system","volume":"205","author":"Grabert","year":"2020","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.celrep.2022.110961_bib21","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"10.1016\/j.celrep.2022.110961_bib22","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.ajhg.2019.03.004","article-title":"Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-pyle disease spectrum and degenerative encephalopathy with brain malformation","volume":"104","author":"Guo","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.celrep.2022.110961_bib23","doi-asserted-by":"crossref","first-page":"E8603","DOI":"10.3390\/ijms21228603","article-title":"Underestimated peripheral effects following pharmacological and conditional genetic microglial depletion","volume":"21","author":"Han","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.celrep.2022.110961_bib24","doi-asserted-by":"crossref","first-page":"e66738","DOI":"10.7554\/eLife.66738","article-title":"Subventricular zone\/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave","volume":"10","author":"Hohsfield","year":"2021","journal-title":"Elife"},{"key":"10.1016\/j.celrep.2022.110961_bib25","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41590-021-00913-5","article-title":"Microglia use TAM receptors to detect and engulf amyloid \u03b2 plaques","volume":"22","author":"Huang","year":"2021","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2022.110961_bib26","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/JLB.MR0519-143R","article-title":"Phenotypic impacts of CSF1R deficiencies in humans and model organisms","volume":"107","author":"Hume","year":"2020","journal-title":"J.\u00a0Leukoc. Biol."},{"key":"10.1016\/j.celrep.2022.110961_bib27","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1042\/CS20170033","article-title":"Animal models of cerebral amyloid angiopathy","volume":"131","author":"J\u00e4kel","year":"2017","journal-title":"Clin. Sci. Lond. Engl."},{"key":"10.1016\/j.celrep.2022.110961_bib28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/alz.12366","article-title":"Prevalence of cerebral amyloid angiopathy: a systematic review and meta-analysis","volume":"18","author":"J\u00e4kel","year":"2021","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.celrep.2022.110961_bib29","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","article-title":"Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer\u2019s disease risk","volume":"51","author":"Jansen","year":"2019","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2022.110961_bib30","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1523\/JNEUROSCI.2110-16.2016","article-title":"Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer\u2019s disease","volume":"37","author":"Jay","year":"2017","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.celrep.2022.110961_bib31","article-title":"Inference and analysis of cell-cell communication using CellChat","author":"Jin","year":"2020","journal-title":"bioRxiv"},{"key":"10.1016\/j.celrep.2022.110961_bib32","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2022.110961_bib33","doi-asserted-by":"crossref","first-page":"828","DOI":"10.14336\/AD.2020.0222","article-title":"TGF-\u03b2 signaling: a therapeutic target to reinstate regenerative plasticity in vascular dementia?","volume":"11","author":"Kandasamy","year":"2020","journal-title":"Aging Dis."},{"key":"10.1016\/j.celrep.2022.110961_bib34","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type Associated with restricting development of Alzheimer\u2019s disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2022.110961_bib35","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat. Methods"},{"key":"10.1016\/j.celrep.2022.110961_bib36","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2022.110961_bib37","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing","volume":"51","author":"Kunkle","year":"2019","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2022.110961_bib89","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"29","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.celrep.2022.110961_bib38","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.neuron.2021.02.010","article-title":"Trem2 restrains the enhancement of tau accumulation and neurodegeneration by \u03b2-amyloid pathology","volume":"109","author":"Lee","year":"2021","journal-title":"Neuron"},{"key":"10.1016\/j.celrep.2022.110961_bib39","doi-asserted-by":"crossref","first-page":"23336","DOI":"10.1073\/pnas.1922788117","article-title":"CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages","volume":"117","author":"Lei","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U\u00a0S\u00a0A"},{"key":"10.1016\/j.celrep.2022.110961_bib40","doi-asserted-by":"crossref","first-page":"11524","DOI":"10.1073\/pnas.1710311114","article-title":"TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy","volume":"114","author":"Leyns","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U\u00a0S\u00a0A"},{"key":"10.1016\/j.celrep.2022.110961_bib41","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2022.110961_bib42","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1126\/science.277.5323.242","article-title":"Pericyte loss and microaneurysm formation in PDGF-B-deficient mice","volume":"277","author":"Lindahl","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.celrep.2022.110961_bib43","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1038\/s41467-018-07295-7","article-title":"Competitive repopulation of an empty microglial niche yields functionally distinct subsets of microglia-like cells","volume":"9","author":"Lund","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2022.110961_bib44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1084\/jem.20120412","article-title":"Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival","volume":"210","author":"Luo","year":"2013","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.celrep.2022.110961_bib45","doi-asserted-by":"crossref","first-page":"113530","DOI":"10.1016\/j.expneurol.2020.113530","article-title":"Microglia depletion increase brain injury after acute ischemic stroke in aged mice","volume":"336","author":"Marino Lee","year":"2021","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.celrep.2022.110961_bib46","doi-asserted-by":"crossref","first-page":"E1316","DOI":"10.1073\/pnas.1525466113","article-title":"The adaptive immune system restrains Alzheimer\u2019s disease pathogenesis by modulating microglial function","volume":"113","author":"Marsh","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U\u00a0S\u00a0A"},{"key":"10.1016\/j.celrep.2022.110961_bib47","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","article-title":"DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors","volume":"8","author":"McGinnis","year":"2019","journal-title":"Cell Syst."},{"key":"10.1016\/j.celrep.2022.110961_bib48","doi-asserted-by":"crossref","first-page":"861","DOI":"10.21105\/joss.00861","article-title":"UMAP: Uniform Manifold approximation and projection","volume":"3","author":"McInnes","year":"2018","journal-title":"J.\u00a0Open Source Softw."},{"key":"10.1016\/j.celrep.2022.110961_bib49","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.jmb.2019.01.045","article-title":"Microglia in Alzheimer\u2019s disease: exploring how genetics and phenotype influence risk","volume":"431","author":"McQuade","year":"2019","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.celrep.2022.110961_bib50","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13024-018-0297-x","article-title":"Development and validation of a simplified method to generate human microglia from pluripotent stem cells","volume":"13","author":"McQuade","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.celrep.2022.110961_bib51","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.1038\/s41467-020-19227-5","article-title":"Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer\u2019s disease","volume":"11","author":"McQuade","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2022.110961_bib52","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1189\/jlb.3RI1116-494R","article-title":"Microglia-driven regulation of oligodendrocyte lineage cells, myelination, and remyelination","volume":"101","author":"Miron","year":"2017","journal-title":"J.\u00a0Leukoc. Biol."},{"key":"10.1016\/j.celrep.2022.110961_bib53","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1093\/hmg\/ddaa182","article-title":"Integrative genomics approach identifies conserved transcriptomic networks in Alzheimer\u2019s disease","volume":"29","author":"Morabito","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.celrep.2022.110961_bib54","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/s41588-021-00894-z","article-title":"Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer\u2019s disease","volume":"53","author":"Morabito","year":"2021","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2022.110961_bib55","first-page":"dev194449","article-title":"CNS macrophages differentially rely on an intronic Csf1r enhancer for their development","volume":"147","author":"Munro","year":"2020","journal-title":"Dev. Camb. Engl."},{"key":"10.1016\/j.celrep.2022.110961_bib56","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.celrep.2022.110961_bib57","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/brain\/awv379","article-title":"Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer\u2019s-like pathology","volume":"139","author":"Olmos-Alonso","year":"2016","journal-title":"Brain J. Neurol."},{"key":"10.1016\/j.celrep.2022.110961_bib58","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41593-018-0296-9","article-title":"Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE","volume":"22","author":"Parhizkar","year":"2019","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.celrep.2022.110961_bib59","doi-asserted-by":"crossref","first-page":"105268","DOI":"10.1016\/j.nbd.2021.105268","article-title":"Analysis of homozygous and heterozygous Csf1r knockout in the rat as a model for understanding microglial function in brain development and the impacts of human CSF1R mutations","volume":"151","author":"Patkar","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.celrep.2022.110961_bib60","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3389\/fimmu.2020.00047","article-title":"Role of macrophage colony-stimulating factor receptor on the proliferation and survival of microglia following systemic nerve and cuprizone-induced injuries","volume":"11","author":"Pons","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.celrep.2022.110961_bib61","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13195-020-00747-7","article-title":"Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer\u2019s disease","volume":"13","author":"Pons","year":"2021","journal-title":"Alzheimer's Res. Ther."},{"key":"10.1016\/j.celrep.2022.110961_bib62","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.4049\/jimmunol.1701783","article-title":"Pleiotropic impacts of macrophage and microglial deficiency on development in rats with targeted mutation of the Csf1r locus","volume":"201","author":"Pridans","year":"2018","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.celrep.2022.110961_bib63","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1359\/jbmr.091009","article-title":"Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in\u00a0vivo","volume":"25","author":"Roelofs","year":"2010","journal-title":"J.\u00a0Bone Miner. Res."},{"key":"10.1016\/j.celrep.2022.110961_bib64","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1038\/s41467-019-11053-8","article-title":"Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations","volume":"10","author":"Rojo","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2022.110961_bib65","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1126\/science.aam8999","article-title":"Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding","volume":"360","author":"Rosenberg","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.celrep.2022.110961_bib66","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuron.2022.03.008","article-title":"Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer\u2019s disease","author":"Sadick","year":"2022","journal-title":"Neuron"},{"key":"10.1016\/j.celrep.2022.110961_bib67","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1038\/ncomms3932","article-title":"Pericyte loss influences Alzheimer-like neurodegeneration in mice","volume":"4","author":"Sagare","year":"2013","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2022.110961_bib68","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","article-title":"Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner","volume":"74","author":"Schafer","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.celrep.2022.110961_bib69","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41588-020-00776-w","article-title":"Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer\u2019s disease risk genes","volume":"53","author":"Schwartzentruber","year":"2021","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2022.110961_bib70","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3233\/JAD-160709","article-title":"APP mutations in cerebral amyloid angiopathy with or without cortical calcifications: report of three Families and a literature review","volume":"56","author":"Sellal","year":"2017","journal-title":"J.\u00a0Alzheimers Dis."},{"key":"10.1016\/j.celrep.2022.110961_bib71","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1084\/jem.20190980","article-title":"Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model","volume":"216","author":"Shi","year":"2019","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.celrep.2022.110961_bib72","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13024-018-0244-x","article-title":"Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer\u2019s disease","volume":"13","author":"Sosna","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.celrep.2022.110961_bib73","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","article-title":"Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer\u2019s disease model","volume":"10","author":"Spangenberg","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2022.110961_bib74","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1093\/brain\/aww016","article-title":"Eliminating microglia in Alzheimer\u2019s mice prevents neuronal loss without modulating amyloid-\u03b2 pathology","volume":"139","author":"Spangenberg","year":"2016","journal-title":"Brain J. Neurol."},{"key":"10.1016\/j.celrep.2022.110961_bib75","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2022.110961_bib76","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1001\/jamaneurol.2014.3889","article-title":"Primary familial brain calcification with known gene mutations: a systematic review and challenges of phenotypic characterization","volume":"72","author":"Tadic","year":"2015","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.celrep.2022.110961_bib77","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00401-016-1547-z","article-title":"The role of APOE in cerebrovascular dysfunction","volume":"131","author":"Tai","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.celrep.2022.110961_bib78","doi-asserted-by":"crossref","first-page":"108189","DOI":"10.1016\/j.celrep.2020.108189","article-title":"Single-nucleus RNA-seq is not suitable for detection of microglial activation genes in humans","volume":"32","author":"Thrupp","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2022.110961_bib79","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1038\/s41598-019-41695-z","article-title":"From Louvain to Leiden: guaranteeing well-connected communities","volume":"9","author":"Traag","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2022.110961_bib80","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/s12974-018-1304-4","article-title":"Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice","volume":"15","author":"Unger","year":"2018","journal-title":"J.\u00a0Neuroinflammation"},{"key":"10.1016\/j.celrep.2022.110961_bib81","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000441919","article-title":"Cerebral \u03b2-amyloid angiopathy is associated with earlier dementia onset in Alzheimer\u2019s disease","volume":"16","author":"Vidoni","year":"2016","journal-title":"Neurodegener. Dis."},{"key":"10.1016\/j.celrep.2022.110961_bib82","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: large-scale single-cell gene expression data analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol."},{"key":"10.1016\/j.celrep.2022.110961_bib83","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13059-019-1663-x","article-title":"PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells","volume":"20","author":"Wolf","year":"2019","journal-title":"Genome Biol."},{"key":"10.1016\/j.celrep.2022.110961_bib84","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.neuron.2016.05.003","article-title":"TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy","volume":"90","author":"Yuan","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.celrep.2022.110961_bib85","doi-asserted-by":"crossref","first-page":"eabc4898","DOI":"10.1126\/sciadv.abc4898","article-title":"Microglia control small vessel calcification via TREM2","volume":"7","author":"Zarb","year":"2021","journal-title":"Sci. Adv."},{"key":"10.1016\/j.celrep.2022.110961_bib86","doi-asserted-by":"crossref","first-page":"11929","DOI":"10.1523\/JNEUROSCI.1860-14.2014","article-title":"An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex","volume":"34","author":"Zhang","year":"2014","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.celrep.2022.110961_bib87","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuron.2015.11.013","article-title":"Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse","volume":"89","author":"Zhang","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.celrep.2022.110961_bib88","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1750-3639.2006.tb00559.x","article-title":"The cerebral beta-amyloid angiopathies: hereditary and sporadic","volume":"16","author":"Zhang-Nunes","year":"2006","journal-title":"Brain Pathol."}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124722007434?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124722007434?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T11:48:03Z","timestamp":1761911283000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124722007434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":89,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["S2211124722007434"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2022.110961","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Absence of microglia promotes diverse pathologies and early lethality in Alzheimer\u2019s disease mice","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2022.110961","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors.","name":"copyright","label":"Copyright"}],"article-number":"110961"}}