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Little is known about the role that microglial CLEC7A signaling plays in AD\u2010related pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We utilized an inducible, central nervous system (CNS) macrophage\u2010specific knockout of\n                      <jats:italic>Clec7a<\/jats:italic>\n                      to evaluate the role of CLEC7A in the 5xFAD mouse model of AD at 5 months of age. We used immunofluorescence microscopy, single\u2010nuclei RNA sequencing, along with biochemical assays, to evaluate plaque burden, microglial activity, and neuronal health.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>CNS macrophage\u2010targeted deletion of CLEC7A in 5xFAD mice led to a twofold increase in plaque burden, exacerbated neuritic dystrophy, and altered the expression of neuronal health genes, but did not appreciably impact microglial activation, plaque engulfment, or disease\u2010associated microglia acquisition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings identify protective roles for CLEC7A in AD\u2010related amyloidosis and suggest that CLEC7A\u2010targeting therapeutics may offer promising strategies for treatment of 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>Conditional loss of CLEC7A in central nervous system (CNS) macrophages of 5xFAD mice results in increased amyloid beta deposition.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Loss of CLEC7A does not alter the disease\u2010associated microglia transcriptional program or affect the recruitment of microglia to plaque surfaces.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Exacerbation of amyloid deposition with loss of CNS\u2010macrophage CLEC7A is associated with worsened neuronal health highlighted by increased neuritic dystrophy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70943","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T17:00:20Z","timestamp":1764349220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Microglial CLEC7A restrains amyloid beta plaque pathology in a mouse model of Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Aman","family":"Mangalmurti","sequence":"first","affiliation":[{"name":"Center for Brain Immunology and Glia (BIG) Department of Neuroscience University of Virginia  Charlottesville Virginia USA"},{"name":"Microbiology, Immunology, and Cancer Biology Graduate Program University of Virginia  Charlottesville Virginia USA"},{"name":"Medical Scientist Training Program School of Medicine University of Virginia  Charlottesville Virginia USA"},{"name":"Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine E.","family":"Zengeler","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia (BIG) Department of Neuroscience University of Virginia  Charlottesville Virginia USA"},{"name":"Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava","family":"Hollis","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia (BIG) Department of Neuroscience University of Virginia  Charlottesville Virginia USA"},{"name":"Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Golden","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia (BIG) Department of Neuroscience University of Virginia  Charlottesville Virginia USA"},{"name":"Medical Scientist Training Program School of Medicine University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Riddlemoser","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia (BIG) Department of Neuroscience University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-0866","authenticated-orcid":false,"given":"John R.","family":"Lukens","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia (BIG) Department of Neuroscience University of Virginia  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