{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:00:28Z","timestamp":1790402428040,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":68,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2022R1I1A1A01053710"],"award-info":[{"award-number":["2022R1I1A1A01053710"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002648","name":"Catholic University of Korea","doi-asserted-by":"publisher","award":["ZC23TISI0860"],"award-info":[{"award-number":["ZC23TISI0860"]}],"id":[{"id":"10.13039\/501100002648","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020621","name":"Seoul St. Mary's Hospital, Catholic University of Korea","doi-asserted-by":"publisher","award":["ZC23TISI0860"],"award-info":[{"award-number":["ZC23TISI0860"]}],"id":[{"id":"10.13039\/501100020621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The classical complement cascade has been implicated in amyloid beta (A\u03b2) clearance and in the pathogenesis of amyloid\u2010related imaging abnormalities (ARIA) during anti\u2010amyloid monoclonal antibody therapy. Clinically accessible peripheral biomarkers of this cascade remain uncharacterized in real\u2010world cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective, hypothesis\u2010generating cohort study of 62 patients with early Alzheimer's disease initiating lecanemab. ARIA risk was evaluated in the safety cohort (\n                      <jats:italic>N<\/jats:italic>\n                      = 62), and absolute amyloid reduction at week 26 was evaluated in the efficacy cohort with paired baseline and 26\u2010week amyloid positron emission tomography (\n                      <jats:italic>N<\/jats:italic>\n                      = 34). Associations of baseline plasma C1q, C3, and apolipoprotein E \u03b54 (\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54) carrier status with these outcomes were examined using Firth's penalized logistic regression and bootstrap linear regression (2000 iterations), with prespecified sensitivity analyses. Within\u2010subject changes in C3 (\n                      <jats:italic>N<\/jats:italic>\n                      = 30) and C1q (\n                      <jats:italic>N<\/jats:italic>\n                      = 19) were assessed by paired Wilcoxon test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Lower baseline C3 was nominally associated with higher ARIA risk (odds ratio [OR] per 1 SD = 0.44, 95% CI: 0.15 to 0.97,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.040, uncorrected), and this association persisted in international normalized ratio (INR)\u2010adjusted and simplified models. C3 \u2264 25th percentile (\u226499\u00a0mg\/dL) showed a trend (OR: 4.78, 95% CI: 0.98 to 26.34,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.052). In the efficacy cohort, higher baseline C1q was associated with smaller amyloid reduction (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = \u22126.86, 95% CI: \u221212.19 to \u22123.06,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002); carriers of at least one\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele, a status that in this cohort jointly reflects genotype and dose\u2010titration, showed less amyloid reduction (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = \u221219.50, 95% CI \u221231.57 to \u22128.40,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Within\u2010subject changes in C1q and C3 were not significant (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.248 and 0.114, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Lower baseline C3 was consistently associated with ARIA risk across sensitivity analyses and higher baseline C1q with smaller amyloid reduction at week 26. Findings are exploratory given the limited single\u2010center sample.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70313","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:35:30Z","timestamp":1788838530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Baseline plasma C1q and C3 as potential biomarkers for lecanemab efficacy and ARIA risk in early Alzheimer's disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Gihwan","family":"Byeon","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung\u2010Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, St. Vincent's Hospital, College of Medicine The Catholic University of Korea  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Hyun","family":"Um","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunggyun","family":"Ha","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Radiology Seoul St. Mary's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya Youngju","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Radiology Yeouido St. Mary's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilah","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul St. Mary's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhee","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul St. Mary's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Uk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Kook","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Research Institute NEUROPHET Inc.  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