{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:12:11Z","timestamp":1789510331164,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T00:00:00Z","timestamp":1728172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Growing evidence suggests a role for neuroinflammation in Alzheimer's disease (AD). We investigated complement pathway activity in AD patient cerebrospinal fluid (CSF) and evaluated its modulation by the anti\u2010tau antibody semorinemab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Immunoassays were applied to measure CSF complement proteins C4, factor B (FB), C3 and their cleavage fragments C4a, C3a, and factor Bb (Bb) in AD patients and a separate cognitively unimpaired (CU) cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>All measured CSF complement proteins were increased in AD versus CU subjects, with C4a displaying the most robust increase. Finally, semorinemab did not have a significant pharmacodynamic effect on CSF complement proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Elevated levels of CSF C4a, C4, C3a, C3, Bb, and FB are consistent with complement activation in AD brains. Despite showing a reduction in CSF soluble tau species, semorinemab did not impact complement protein levels or activity. Further studies are needed to determine the value of complement proteins as neuroinflammation biomarkers in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Cerebrospinal fluid (CSF) complement proteins C4a, C3a, Bb, C4, C3, and factor B levels were increased in Alzheimer's disease (AD) patients compared to a separate cognitively unimpaired (CU) cohort.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Baseline CSF complement protein levels were correlated with neuro\u2010axonal degeneration and glial activation biomarkers in AD patients.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The investigational anti\u2010tau antibody semorinemab did not impact CSF complement protein levels or activity relative to the placebo arm.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14271","type":"journal-article","created":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T04:18:50Z","timestamp":1728188330000},"page":"7940-7953","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["CSF complement proteins are elevated in prodromal to moderate Alzheimer's disease patients and are not altered by the anti\u2010tau antibody semorinemab"],"prefix":"10.1002","volume":"20","author":[{"given":"Cosme","family":"Sandoval","sequence":"first","affiliation":[{"name":"Department of Translational Medicine Genentech Inc OMNI  South San Francisco California 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