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Complement\u2010mediated synaptic pruning has been associated with this excessive loss of synapses in AD. Here, we investigated the effect of C5aR1 inhibition on microglial and astroglial synaptic pruning in two mouse models of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A combination of super\u2010resolution and confocal and tridimensional image reconstruction was used to assess the effect of genetic ablation or pharmacological inhibition of C5aR1 on the Arctic48 and Tg2576 models of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Genetic ablation or pharmacological inhibition of C5aR1 partially rescues excessive pre\u2010synaptic pruning and synaptic loss in an age and region\u2010dependent fashion in two mouse models of AD, which correlates with improved long\u2010term potentiation (LTP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Reduction of excessive synaptic pruning is an additional beneficial outcome of the suppression of C5a\u2010C5aR1 signaling, further supporting its potential as an effective targeted therapy to treat 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>C5aR1 ablation restores long\u2010term potentiation in the Arctic model of AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>C5aR1 ablation rescues region specific excessive pre\u2010synaptic loss.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>C5aR1 antagonist, PMX205, rescues VGlut1 loss in the Tg2576 model of AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>C1q tagging is not sufficient to induce VGlut1 microglial ingestion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Astrocytes contribute to excessive pre\u2010synaptic loss at late stages of the disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13682","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T20:04:20Z","timestamp":1706299460000},"page":"2173-2190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["C5aR1 signaling promotes region\u2010 and age\u2010dependent synaptic pruning in models of Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Angela","family":"Gomez\u2010Arboledas","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enik\u00f6","family":"Kramar","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Hui","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry University of California  Irvine California 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