{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:12:07Z","timestamp":1789603927680,"version":"build-2803163510"},"reference-count":56,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2023,11,21]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Numerous studies have shown that the complement system plays an important role in Alzheimer\u2019s disease (AD). However, whether complement 4 (C4) protein in cerebrospinal fluid (CSF) was associated with AD pathology, especially in the early stage of AD, is still unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We aimed to explore the association of CSF C4 with AD pathology and cognition in the preclinical AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      The study included a total of 287 participants from the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI) database. Based on the A\/T scheme, they were divided into four groups to access the changes of CSF C4 in the preclinical AD. Linear regression models were used to test the associations between CSF C4 and AD core biomarkers, namely A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      , P-tau, and T-tau.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The level of CSF C4 decreased in the A\u200a+\u200aT- group compared with the A-T- group ( p\u200a=\u200a0.04) and it increased in the A-T+ group compared to the A\u200a+\u200aT- group ( p\u200a=\u200a0.01). In pooled samples, C4 was significantly associated with AD core biomarkers (all p\u200a&lt;\u200a0.05), but only in the A\u200a+\u200agroup after stratification according to the A\/T scheme. Furthermore, CSF C4 levels at baseline were associated with longitudinal cognitive changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our results showed that CSF C4 levels changed dynamically in the preclinical AD, and that the responses of CSF C4 to brain A\u03b2 pathology, tau pathology and neurodegeneration were found only in the presence of amyloid plaques, both of which indicates the complex link between C4 and AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230513","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T11:19:43Z","timestamp":1700565583000},"page":"1071-1081","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Cerebrospinal Fluid Complement 4 Levels Were Associated with Alzheimer\u2019s Disease Pathology and Cognition in Non-Demented Elderly"],"prefix":"10.1177","volume":"96","author":[{"given":"Jie","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China"},{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270502"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.3.355"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu190"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201709069"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abi8593"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(96)00108-X"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02024-8"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1038\/nature16549"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90040-0"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1984.tb02052.x"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5769(01)00019-4"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00763-8"},{"key":"ref016","first-page":"381","volume":"50","author":"Pardi\u00f1as AF","year":"2018","journal-title":"NatGenet"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1038\/ng.940"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi8654"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721000179"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.03.007"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181cb3e25"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2017.10.004"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.141.11.1356"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1177\/1073191121991215"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.140.6.566"},{"key":"ref026","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1017\/S1041610297004870","volume":"9","author":"Morris JC","year":"1997","journal-title":"Int Psychogeriatr"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1159\/000109754"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2006.05.2347"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.12.1696"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.09.009"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201400178"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01174-0"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0301-5"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.1037\/a0020761"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0662-9"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687336"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0536-8"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.1007\/BF00685397"},{"key":"ref042","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10016"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(92)90017-6"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90843-4"},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.12.016"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"ref047","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt266"},{"key":"ref048","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-022-01409-5"},{"key":"ref049","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80356-8"},{"key":"ref050","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8723-8"},{"key":"ref051","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.06.021"},{"key":"ref052","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012308"},{"key":"ref053","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01910-4"},{"key":"ref054","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01266-z"},{"key":"ref055","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12607"},{"key":"ref056","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.274"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-230513","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-230513","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-230513","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:44Z","timestamp":1777370924000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-230513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,4]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,11,21]]}},"alternative-id":["10.3233\/JAD-230513"],"URL":"https:\/\/doi.org\/10.3233\/jad-230513","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,4]]}}}