{"id":"https://openalex.org/W7212224407","doi":"https://doi.org/10.64898/2026.09.09.750237","title":"Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer\u2019s Disease","display_name":"Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer\u2019s Disease","publication_year":2026,"publication_date":"2026-09-10","ids":{"openalex":"https://openalex.org/W7212224407","doi":"https://doi.org/10.64898/2026.09.09.750237","pmid":"https://pubmed.ncbi.nlm.nih.gov/42818366","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13622655"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.09.750237","doi":"https://doi.org/10.64898/2026.09.09.750237","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.09.750237","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/10/2026.09.09.750237.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/10/2026.09.09.750237.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5054430118","display_name":"Collin J. Nadarajah","orcid":"https://orcid.org/0000-0001-7275-4723","observed_orcids":["https://orcid.org/0000-0001-7275-4723"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Collin J. Nadarajah","raw_affiliation_strings":["Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064325494","display_name":"Michelle Y. Li","orcid":"https://orcid.org/0009-0007-5155-0546","observed_orcids":["https://orcid.org/0009-0007-5155-0546"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michelle Y. Li","raw_affiliation_strings":["Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039802209","display_name":"Sohui Park","orcid":"https://orcid.org/0000-0003-1952-0893","observed_orcids":["https://orcid.org/0000-0003-1952-0893"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sohui Park","raw_affiliation_strings":["Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034276774","display_name":"Jennifer H. Lawrence","orcid":"https://orcid.org/0000-0002-3501-7262","observed_orcids":["https://orcid.org/0000-0002-3501-7262"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jennifer H. Lawrence","raw_affiliation_strings":["Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5151329894","display_name":"Ashish Sharma","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ashish Sharma","raw_affiliation_strings":["Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057057662","display_name":"Emma Danhash","orcid":"https://orcid.org/0000-0002-0737-9311","observed_orcids":["https://orcid.org/0000-0002-0737-9311"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Emma P. Danhash","raw_affiliation_strings":["Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010166794","display_name":"Celeste M M. Karch","orcid":"https://orcid.org/0000-0002-6854-5547","observed_orcids":["https://orcid.org/0000-0002-6854-5547"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Celeste M. Karch","raw_affiliation_strings":["Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5029790388","display_name":"Erik S. Musiek","orcid":"https://orcid.org/0000-0002-8873-0360","observed_orcids":["https://orcid.org/0000-0002-8873-0360"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]},{"id":"https://openalex.org/I4210123851","display_name":"Hope Center for Neurological Disorders","ror":"https://ror.org/035nzyk88","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210123851"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Erik S. Musiek","raw_affiliation_strings":["Center On Biological Rhythms And Sleep and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA","Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":"https://orcid.org/0000-0002-8873-0360","affiliations":[{"raw_affiliation_string":"Center On Biological Rhythms And Sleep and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549","https://openalex.org/I4210123851"]},{"raw_affiliation_string":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5029790388"],"corresponding_institution_ids":["https://openalex.org/I204465549","https://openalex.org/I4210123851"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9028000235557556,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9028000235557556,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11266","display_name":"Neuroinflammation and Neurodegeneration Mechanisms","score":0.09120000153779984,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10993","display_name":"Complement system in diseases","score":0.003100000089034438,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/complement-c4","display_name":"complement C4","score":0.9169999957084656},{"id":"https://openalex.org/keywords/alzheimer-s-disease","display_name":"Alzheimer's disease","score":0.8500000238418579},{"id":"https://openalex.org/keywords/amyloid-plaques","display_name":"amyloid plaques","score":0.9819999933242798},{"id":"https://openalex.org/keywords/5xfad-mice","display_name":"5xFAD mice","score":0.7599999904632568},{"id":"https://openalex.org/keywords/disease-associated-microglia","display_name":"disease-associated microglia","score":0.8939999938011169},{"id":"https://openalex.org/keywords/microglial-activation","display_name":"microglial activation","score":0.8230000138282776},{"id":"https://openalex.org/keywords/neuroinflammation","display_name":"neuroinflammation","score":0.9380000233650208},{"id":"https://openalex.org/keywords/astrocytes","display_name":"astrocytes","score":0.7799999713897705},{"id":"https://openalex.org/keywords/complement-system","display_name":"complement system","score":0.6179999709129333},{"id":"https://openalex.org/keywords/amyloidosis","display_name":"amyloidosis","score":0.6209999918937683}],"concepts":[{"id":"https://openalex.org/C2779830541","wikidata":"https://www.wikidata.org/wiki/Q1622829","display_name":"Microglia","level":3,"score":0.732699990272522},{"id":"https://openalex.org/C111684460","wikidata":"https://www.wikidata.org/wiki/Q334848","display_name":"Complement system","level":3,"score":0.6725000143051147},{"id":"https://openalex.org/C87753298","wikidata":"https://www.wikidata.org/wiki/Q17157137","display_name":"Neuroinflammation","level":3,"score":0.592199981212616},{"id":"https://openalex.org/C136449434","wikidata":"https://www.wikidata.org/wiki/Q428253","display_name":"Innate immune system","level":3,"score":0.5404999852180481},{"id":"https://openalex.org/C2777633098","wikidata":"https://www.wikidata.org/wiki/Q2736051","display_name":"Amyloid (mycology)","level":2,"score":0.534600019454956},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.492000013589859},{"id":"https://openalex.org/C502032728","wikidata":"https://www.wikidata.org/wiki/Q11081","display_name":"Alzheimer's disease","level":3,"score":0.45509999990463257},{"id":"https://openalex.org/C2780029684","wikidata":"https://www.wikidata.org/wiki/Q14891716","display_name":"Serum amyloid P component","level":4,"score":0.44670000672340393},{"id":"https://openalex.org/C141035611","wikidata":"https://www.wikidata.org/wiki/Q5532934","display_name":"Genetically modified mouse","level":4,"score":0.4397999942302704},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.4309999942779541},{"id":"https://openalex.org/C182704531","wikidata":"https://www.wikidata.org/wiki/Q1364740","display_name":"Knockout mouse","level":3,"score":0.4165000021457672},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3968000113964081},{"id":"https://openalex.org/C2776925932","wikidata":"https://www.wikidata.org/wiki/Q1755122","display_name":"Neurodegeneration","level":3,"score":0.38280001282691956},{"id":"https://openalex.org/C2779685842","wikidata":"https://www.wikidata.org/wiki/Q18040973","display_name":"TREM2","level":4,"score":0.3788999915122986},{"id":"https://openalex.org/C31705614","wikidata":"https://www.wikidata.org/wiki/Q423510","display_name":"Amyloid precursor protein","level":4,"score":0.3400999903678894},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.33980000019073486},{"id":"https://openalex.org/C171279029","wikidata":"https://www.wikidata.org/wiki/Q5128320","display_name":"Classical complement pathway","level":4,"score":0.32010000944137573},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.31940001249313354},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.31540000438690186},{"id":"https://openalex.org/C180081513","wikidata":"https://www.wikidata.org/wiki/Q4914721","display_name":"Biochemistry of Alzheimer's disease","level":5,"score":0.29679998755455017},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.2888000011444092},{"id":"https://openalex.org/C175773311","wikidata":"https://www.wikidata.org/wiki/Q5156412","display_name":"Complement receptor","level":4,"score":0.2872999906539917},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.287200003862381},{"id":"https://openalex.org/C2776156579","wikidata":"https://www.wikidata.org/wiki/Q417667","display_name":"Amyloid beta","level":3,"score":0.287200003862381},{"id":"https://openalex.org/C2777790613","wikidata":"https://www.wikidata.org/wiki/Q191562","display_name":"Cerebral amyloid angiopathy","level":4,"score":0.287200003862381},{"id":"https://openalex.org/C2779244956","wikidata":"https://www.wikidata.org/wiki/Q184204","display_name":"Macrophage","level":3,"score":0.2867000102996826},{"id":"https://openalex.org/C189446657","wikidata":"https://www.wikidata.org/wiki/Q4736500","display_name":"Alternative complement pathway","level":4,"score":0.2833999991416931},{"id":"https://openalex.org/C2777427615","wikidata":"https://www.wikidata.org/wiki/Q954257","display_name":"Degenerative disease","level":3,"score":0.27410000562667847},{"id":"https://openalex.org/C71318922","wikidata":"https://www.wikidata.org/wiki/Q426181","display_name":"Complement component 5","level":4,"score":0.27320000529289246},{"id":"https://openalex.org/C2779951007","wikidata":"https://www.wikidata.org/wiki/Q816798","display_name":"Amyloidosis","level":2,"score":0.2703999876976013},{"id":"https://openalex.org/C90582226","wikidata":"https://www.wikidata.org/wiki/Q424292","display_name":"Anaphylatoxin","level":4,"score":0.2689000070095062},{"id":"https://openalex.org/C179369057","wikidata":"https://www.wikidata.org/wiki/Q20970075","display_name":"Complement factor I","level":4,"score":0.26579999923706055},{"id":"https://openalex.org/C2778609137","wikidata":"https://www.wikidata.org/wiki/Q105790271","display_name":"Myelin","level":3,"score":0.26109999418258667},{"id":"https://openalex.org/C2780884517","wikidata":"https://www.wikidata.org/wiki/Q177105","display_name":"Neuroglia","level":3,"score":0.25859999656677246},{"id":"https://openalex.org/C2778560701","wikidata":"https://www.wikidata.org/wiki/Q14914188","display_name":"Neuregulin 1","level":3,"score":0.257999986410141},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.2522999942302704}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.64898/2026.09.09.750237","doi":"https://doi.org/10.64898/2026.09.09.750237","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.09.750237","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/10/2026.09.09.750237.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmh:oai:pubmedcentral.nih.gov:13622655","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13622655/","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13622655/pdf/nihpp-2026.09.09.750237v1.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bioRxiv","raw_type":"Text"},{"id":"pmid:42818366","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42818366","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bioRxiv : the preprint server for biology","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.64898/2026.09.09.750237","doi":"https://doi.org/10.64898/2026.09.09.750237","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.09.750237","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/10/2026.09.09.750237.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9537000060081482,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G6290719334","display_name":"Role of REV-ERB Proteins in Neuroinflammation and Alzheimer's Disease","funder_award_id":"R01AG063743","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G9000874052","display_name":"ROLE OF GLIAL CIRCADIAN CLOCK DYSFUNCTION IN THE PATHOGENESIS OF ALZHEIMER'S DISEASE","funder_award_id":"R01AG054517","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"}],"funders":[{"id":"https://openalex.org/F4320311176","display_name":"Children's Discovery Institute","ror":"https://ror.org/02swjdp46"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320333635","display_name":"Center for Cellular Imaging, Washington University","ror":null},{"id":"https://openalex.org/F4320337337","display_name":"National Institute on Aging","ror":"https://ror.org/049v75w11"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7212224407.pdf","grobid_xml":"https://content.openalex.org/works/W7212224407.grobid-xml"},"referenced_works_count":1,"referenced_works":["https://openalex.org/W4404224839"],"related_works":["https://openalex.org/W2035355245","https://openalex.org/W2002774469","https://openalex.org/W655965326","https://openalex.org/W1979958331","https://openalex.org/W4410859542","https://openalex.org/W2238460669","https://openalex.org/W2047658053","https://openalex.org/W1974930618","https://openalex.org/W4415273408","https://openalex.org/W2765263791"],"abstract_inverted_index":{"Abstract":[0],"The":[1],"complement":[2,29,49,57,83,245],"system,":[3],"a":[4,78,112,176,190,204,212,251,261],"proteolytic":[5],"cascade":[6,246],"crucial":[7],"for":[8,192,264],"innate":[9],"immune":[10],"system":[11],"function,":[12],"is":[13,60],"dysregulated":[14],"in":[15,54,65,67,81,96,106,135,143,154,158,167,178,184,194,199,227,231],"brain":[16,141],"aging":[17,71],"and":[18,33,37,44,72,180,247,258,260],"neurodegenerative":[19],"diseases,":[20],"including":[21,31],"Alzheimer":[22],"Disease":[23],"(AD).":[24],"In":[25],"models":[26],"of":[27,41,46,70,90,94,104,125,164,189,207,254],"AD,":[28],"proteins,":[30],"C1q":[32],"C3,":[34],"are":[35],"upregulated":[36,64],"mediate":[38],"microglial":[39,229],"clearance":[40],"amyloid":[42,73,107,136],"plaques":[43],"pruning":[45],"synapses.":[47],"Among":[48],"genes,":[50],"C4b":[51,115],",":[52],"which":[53,170],"mice":[55,146],"encodes":[56],"protein":[58],"C4,":[59],"the":[61,68,82,91,102,121,208,243],"most":[62],"highly":[63],"astrocytes":[66],"setting":[69],"pathology.":[74,99],"While":[75],"C4":[76,95,105,193,221,238],"plays":[77],"key":[79,252],"role":[80,93,191],"cascade,":[84],"there":[85],"have":[86,240],"been":[87],"no":[88],"investigations":[89],"direct":[92],"regulating":[97,195,228],"AD":[98,168],"To":[100,128],"probe":[101],"function":[103,257],"plaque-related":[108],"pathology,":[109],"we":[110,131,174,202],"crossed":[111],"germ":[113],"line":[114],"knockout":[116],"mouse":[117,123],"(C4":[118],"KO)":[119],"to":[120,148,161,211],"5XFAD":[122,150],"model":[124],"AD-related":[126,255],"amyloidosis.":[127],"our":[129,234],"surprise,":[130],"observed":[132,175,203],"striking":[133],"reductions":[134],"plaque":[137,155],"pathology":[138,259],"across":[139],"multiple":[140],"regions":[142],"5XFAD-C4":[144,185],"KO":[145,186],"relative":[147],"standard":[149],"controls.":[151],"This":[152],"reduction":[153,177],"burden":[156],"stands":[157],"sharp":[159],"contrast":[160],"previous":[162],"reports":[163],"C3":[165],"deletion":[166],"models,":[169],"increases":[171],"plaques.":[172],"Additionally,":[173],"neuroinflammation":[179],"peri-plaque":[181,209],"glial":[182,256],"clustering":[183],"mice,":[187],"suggestive":[188],"overall":[196],"neuroinflammatory":[197],"tone":[198],"AD.":[200,232],"Finally,":[201],"phenotypic":[205],"shift":[206],"microglia":[210,216],"more":[213],"reactive":[214],"disease-associated":[215],"(DAM)":[217],"phenotype,":[218],"indicating":[219],"that":[220,237],"could":[222],"be":[223],"an":[224],"important":[225],"factor":[226],"reactivity":[230],"Altogether,":[233],"results":[235],"demonstrate":[236],"may":[239,248],"functions":[241],"beyond":[242],"classical":[244],"serve":[249],"as":[250],"facilitator":[253],"possible":[262],"target":[263],"therapeutic":[265],"modification.":[266]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-12T00:00:00"}