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On the other hand, elimination of microglia shifts amyloid beta (A\u03b2) accumulation from parenchymal plaques to cerebral amyloid angiopathy (CAA), mimicking the effects of global APOE*4 knock\u2010in. Here, we specifically knock\u2010out microglial\u2010expressed ApoE while keeping astrocytic\u2010expressed ApoE intact. When microglial\u2010specific ApoE is knocked\u2010out of a 5xFAD mouse model of AD, we found a\u2009~35% increase in average A\u03b2 plaque size, but no changes in plaque load, microglial number, microglial clustering around A\u03b2 plaques, nor the formation of CAA. Immunostaining revealed ApoE protein present in plaque\u2010associated microglia in 5xFAD mice with microglial\u2010specific ApoE knockout, suggesting that microglia can take up ApoE from other cellular sources. Mice with\n                    <jats:italic>Apoe<\/jats:italic>\n                    knocked\u2010out of microglia had lower synaptic protein levels than control mice, indicating that microglial\u2010expressed ApoE may have a role in synapse maintenance. Surprisingly, microglial\u2010specific ApoE knock\u2010out resulted in few differentially expressed genes in both 5xFAD and control mice; however, some rescue of 5xFAD associated neuronal networks may occur with microglial\u2010specific ApoE knock\u2010out as shown by weighted gene co\u2010expression analysis. Altogether, our data indicates that microglial\u2010expressed ApoE may not be necessary for plaque formation or for the microglial transcriptional shift into a Disease Associated Microglia state that is associated with reactivity to plaques but may be necessary for plaque homeostasis in disease and synaptic maintenance under normal conditions.\n                  <\/jats:p>","DOI":"10.1002\/glia.24105","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T02:24:12Z","timestamp":1634437452000},"page":"287-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Microglia\u2010specific\n                    <scp>ApoE<\/scp>\n                    knock\u2010out does not alter Alzheimer's disease plaque pathogenesis or gene expression"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9062-8672","authenticated-orcid":false,"given":"Caden 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