{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:50:15Z","timestamp":1793116215322,"version":"4.5.0"},"reference-count":99,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG061729"],"award-info":[{"award-number":["R01 AG061729"]}],"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":["R01 AG085545"],"award-info":[{"award-number":["R01 AG085545"]}],"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":["T32AG021890"],"award-info":[{"award-number":["T32AG021890"]}],"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":["P30 AG066546"],"award-info":[{"award-number":["P30 AG066546"]}],"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":["P30 AG013319"],"award-info":[{"award-number":["P30 AG013319"]}],"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":["P30 AG044271"],"award-info":[{"award-number":["P30 AG044271"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020114","name":"Methodist Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020114","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013030","name":"William and Ella Owens Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013030","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"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Innate immune activation plays a crucial role in the pathogenesis of Alzheimer's disease (AD) and related dementias (ADRD). The cytosolic DNA sensing pathway, involving cGAMP synthase (cGAS) and Stimulator of Interferon Genes (STING), has emerged as a key mediator of neurodegenerative diseases. However, the precise mechanisms through which cGAS activation influences AD progression remain poorly understood. In this study, we observed significant up\u2010regulation of cGAS\u2010STING signaling pathway in AD. Notably, this increase is primarily attributed to microglia, rather than non\u2010microglial cell types. Using an inducible, microglia\u2010specific cGAS knockout mouse model in the 5xFAD background, we demonstrated that deleting microglial cGAS at the onset of amyloid\u2010\u03b2 (A\u03b2) pathology profoundly restricts plaque accumulation and protects mice from A\u03b2\u2010induced cognitive impairment. Mechanistically, our study revealed cGAS promotes plaque\u2010associated microglia accumulation and is essential for inflammasome activation. Moreover, we showed that restricting cGAS\u2010mediated innate immunity is crucial for preserving inter\u2010cellular communication in the brain and induces pleiotrophin, a neuroprotective factor. These findings offer novel insights into the specific roles of the innate immune system in AD employing a cell\u2010type\u2010specific approach. The\u00a0conclusions provide a foundation for targeted interventions to modulate the microglial cGAS\u2010STING signaling pathway, offering promising therapeutic strategy for AD treatment.<\/jats:p>","DOI":"10.1002\/advs.202410910","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T13:55:17Z","timestamp":1738763717000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid\u2010\u03b2\u2010Induced Pathogenesis of Alzheimer's Disease"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3786-8770","authenticated-orcid":false,"given":"Sijia","family":"He","sequence":"first","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"},{"name":"Department of Cellular and Integrative Physiology University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namrata","family":"Mittra","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindita","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Wang","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Song","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"},{"name":"Division of Endocrinology Department of Medicine University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Metabolic Syndrome Research Center The Second Xiangya Hospital of Central South University  Changsha Hunan 410011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-2413","authenticated-orcid":false,"given":"Xianlin","family":"Han","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"},{"name":"Division of Diabetes Department of Medicine University of Texas Health Science Center at San Antonio  San Antonio TX 78229 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ssmph.2022.101052"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000911"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.006"},{"key":"e_1_2_10_2_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.05.014"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.10.016"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232458"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-021-00869-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3558"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705499114"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1006-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180139"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1621363114"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21239249"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204058119"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.020"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.710608"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06373-1"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00337-2"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01315-6"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2024.08.001"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13171426"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.4c00392"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-023-00185-8"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08620-4"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41892-5"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.028"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2002144117"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.08.039"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2022.0316"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.013"},{"key":"e_1_2_10_25_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25125-1"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11674-z"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-022-01721-1"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.003"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00951-0"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25158"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.02.014"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-014-9413-8"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.5274"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1558-9"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7176"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0695-9"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603243104"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI155096"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.08.006"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.010"},{"key":"e_1_2_10_40_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2023.102703"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X13666150716165726"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(91)90609-V"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00391-w"},{"key":"e_1_2_10_43_3","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0433-4"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-12-03783.1991"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01795-8"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110961"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142322"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0296-9"},{"key":"e_1_2_10_47_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.016"},{"key":"e_1_2_10_47_4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710311114"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00394-4"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.02.010"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2110-16.2016"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0216-6"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20212479"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2018.1558682"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01295-y"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0297-1"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.749587"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0616-08.2008"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23074"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.11.14.623651"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00997.x"},{"key":"e_1_2_10_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1332"},{"key":"e_1_2_10_58_3","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00488-7"},{"key":"e_1_2_10_58_4","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2024.0676"},{"key":"e_1_2_10_58_5","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.371368"},{"key":"e_1_2_10_58_6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010233"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113022"},{"key":"e_1_2_10_60_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2001.2705"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt273"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80324-4"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034406"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22389"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-070918-050306"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-021-01054-y"},{"key":"e_1_2_10_67_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210523"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.170"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.12.025"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01685-z"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0844-5"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202410910","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202410910","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202410910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T15:41:33Z","timestamp":1789746093000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202410910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":99,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/advs.202410910"],"URL":"https:\/\/doi.org\/10.1002\/advs.202410910","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"assertion":[{"value":"2024-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2410910"}}