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Hillblom Foundation","doi-asserted-by":"publisher","award":["2021\u2010A\u2010020\u2010FEL"],"award-info":[{"award-number":["2021\u2010A\u2010020\u2010FEL"]}],"id":[{"id":"10.13039\/100001167","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    C1q is a multifunctional protein, including its role as the initiating protein of the classical complement cascade. While classical pathway activation is involved in synaptic pruning during nervous system development, it also contributes to inflammation and cognitive decline in Alzheimer's disease (AD). Constitutive genetic C1q deficiency has been shown to reduce glial activation and attenuate neuronal loss in AD mouse models, but the specific contributions of microglial C1q to AD pathology while avoiding deficits during post\u2010natal development remain unaddressed. To dissect specific role(s) of microglial C1q in AD progression, we crossed the Cx3cr1\n                    <jats:sup>CreERT2<\/jats:sup>\n                    mouse model that deletes C1q from microglia in young adulthood (8\u2009weeks of age) to the aggressive Arctic48 (Arc) amyloidosis mouse model. At 10\u2009months, young adult microglial C1q deletion (Arc C1q\n                    <jats:sup>\u0394MG<\/jats:sup>\n                    ) was associated with improved spatial memory performance, despite unchanged amyloid plaque burden. Furthermore, Arc C1q\n                    <jats:sup>\u0394MG<\/jats:sup>\n                    mice exhibited reduced hippocampal C3 protein levels without altering C3 mRNA. No changes were observed in C5aR1, astrocyte GFAP, or microglial Iba1 protein expression. However, Arc C1q\n                    <jats:sup>\u0394MG<\/jats:sup>\n                    mice demonstrated region specific reductions in microglial synaptic engulfment, alongside decreased phagolysosome\u2010associated amyloid in both microglia and astrocytes, and reduced hippocampal amyloid compaction. These findings support a role for C1q in astrocytic C3 induction and the engulfment of both synapses and amyloid. Importantly, young adult microglial C1q inhibition confers cognitive benefits without exacerbating amyloid pathology, suggesting a therapeutic window in which targeting microglial C1q may help preserve synaptic integrity and modulate the neuroinflammatory processes during the later stages of AD.\n                  <\/jats:p>","DOI":"10.1002\/glia.70189","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:30:58Z","timestamp":1784014258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Young Adult Microglial Deletion of C1q Reduces Engulfment of Synapses and Partially Mitigates Cognitive Impairment in an Aggressive Alzheimer's Disease Mouse Model"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4664-2853","authenticated-orcid":false,"given":"Tiffany J.","family":"Petrisko","sequence":"first","affiliation":[{"name":"Department of Molecular Biology &amp; Biochemistry University of California, Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3779-6412","authenticated-orcid":false,"given":"Shu\u2010Hui","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Biochemistry University of California, Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-9512","authenticated-orcid":false,"given":"Angela","family":"Gomez\u2010Arboledas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Biochemistry University of California, Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5205-4233","authenticated-orcid":false,"given":"Blossom","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Biochemistry University of California, Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3000-024X","authenticated-orcid":false,"given":"Andrea J.","family":"Tenner","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Biochemistry University of California, Irvine  Irvine California USA"},{"name":"Department of Neurobiology and Behavior University of California Irvine  Irvine California USA"},{"name":"Department of Pathology and Laboratory Medicine University of California, Irvine, School of Medicine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1996.0043"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3087475"},{"key":"e_1_2_11_4_1","first-page":"1552","article-title":"2025 Alzheimer's Disease Facts and Figures","volume":"21","author":"Alzheimer's Association","year":"2025","journal-title":"Alzheimer's & Dementia"},{"key":"e_1_2_11_5_1","unstructured":"Annexon Biosciences.2024.\u201cTopline Results From Phase 3 Study of ANX005 in Guillain\u2010Barr\u00e9 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