{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:08:01Z","timestamp":1793833681564,"version":"4.6.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research","doi-asserted-by":"publisher","award":["R01-NS120417, R01-AI160737, P30-AG072958"],"award-info":[{"award-number":["R01-NS120417, R01-AI160737, P30-AG072958"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Dectin-1, encoded by\n                      <jats:italic>Clec7a<\/jats:italic>\n                      , is highly expressed in disease-associated microglia in Alzheimer\u2019s disease (AD), yet its\n                      <jats:italic>in vivo<\/jats:italic>\n                      function remains largely unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated\n                      <jats:italic>Clec7a<\/jats:italic>\n                      -floxed mice and conditionally deleted dectin-1 in microglia to determine its effects on pathology and behavior using the 5xFAD mice model. No dectin-1 ligand injection was used. Amyloid pathology, immune phenotypes in the brain, and behavior were examined across disease stages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 6-month (mo) old mice, microglial dectin-1 reduced dense A\u03b2 plaques in the subiculum without detectable behavioral effects. At 9-mo, microglial dectin-1 impaired memory retention and spatial learning, accompanied by an increased diffuse\/dense A\u03b2 plaque ratio in the hilus of the dentate gyrus and limited brain infiltration of Ly6G\n                      <jats:sup>lo<\/jats:sup>\n                      neutrophils. At 16-mo, microglial dectin-1 increased freezing behavior suggestive of heightened emotional reactivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Microglial dectin-1 exerts age-dependent effects: beneficial for amyloid pathology in mid-life but detrimental for cognition and anxiety-related behavior in later life. These context-specific outcomes highlight the need to consider age, the cell types expressing dectin-1, and dectin-1-activating ligands. Future studies should define the classes of ligands and signaling landscape of microglial dectin-1 across the disease course with the goal of identifying windows where intervention could tilt its function toward sustained neuroprotection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1864888","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:10Z","timestamp":1788412930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Microglial dectin-1\/Clec7a in an alzheimer\u2019s disease model: a double-edged sword across the lifespan"],"prefix":"10.3389","volume":"17","author":[{"given":"Wen","family":"Xi","sequence":"first","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona 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