{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:40:20Z","timestamp":1783521620246,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["A2023020F"],"award-info":[{"award-number":["A2023020F"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>While the anti\u2010amyloid\u2010lowering immunotherapies provide the first disease\u2010targeting therapies for the treatment of Alzheimer's disease, there remain harmful adverse events causing hesitation among patients, families, physicians, and regulatory bodies. Though these drugs have been repeatedly proven to lower brain amyloid plaque burden, the specific cellular mechanisms and pathways by which the immunotherapy impacts the brain remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This study aimed to transcriptionally profile the brain's immediate immune response to anti\u2010amyloid beta (anti\u2010A\u03b2) antibodies. To evaluate acute cellular priorities, we intracranially injected anti\u2010A\u03b2 antibody (3D6) or an isotype\u2010matched control immunoglobulin G (IgG) antibody and performed single\u2010cell sequencing analysis after 3 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We found reduced numbers of a motile microglia cluster and homeostatic microglia in the 3D6 antibody\u2010injected cortex compared to the IgG\u2010injected cortex. It was also found that chemokine\/cytokine signaling was enriched across homeostatic\u2010proinflammatory microglia, interferon\u2010responding microglia, and disease\u2010associated microglia 2 (DAM2) following 3D6 antibody injection. We explored \u201cCCL\u201d signaling, which suggested a change in outgoing signaling coordinated by all microglia types targeting homeostatic microglia, surprisingly not targeting DAM1 or DAM2. We then analyzed enriched signaling pathways clustered by k\u2010means river plots and identified pathways enriched and dampened with acute 3D6 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Together these data supply evidence for significant involvement of microglia in the anti\u2010A\u03b2 response in the brain after just 3 days. Most interestingly, there are changes in cytokine\/chemokine signaling across microglia subtypes, specifically with communication in CCL pathways targeting homeostatic microglia and T cells. These acute signaling changes provide novel insights and generate unique hypotheses on the brain's immediate immune reaction to anti\u2010A\u03b2 antibody.<\/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>Intracranially injected anti\u2010amyloid beta (anti\u2010A\u03b2) antibody promotes an immediate microglial response.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>3D6 exposure resulted in fewer homeostatic and motile microglia subtypes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Acute 3D6 enriches for chemokine\/cytokine signaling pathways.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70201","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T05:16:22Z","timestamp":1768022182000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute anti\u2010A\u03b2 antibody exposure induces microglial changes and significantly alters chemokine signaling"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5110-238X","authenticated-orcid":false,"given":"Kate E.","family":"Foley","sequence":"first","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Neurology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica 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