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ApoE is produced by both astrocytes and microglia in the brain, whereas hepatocytes produce the majority of apoE found in the periphery. Studies using\n                      <jats:italic>APOE<\/jats:italic>\n                      knock-in and transgenic mice have demonstrated a strong isoform-dependent effect of apoE on the accumulation of amyloid-\u03b2 (A\u03b2) deposition in the brain in the form of both A\u03b2-containing amyloid plaques and cerebral amyloid angiopathy. However, the specific contributions of different apoE pools to AD pathogenesis remain unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We have begun to address these questions by generating new lines of\n                      <jats:italic>APOE<\/jats:italic>\n                      knock-in (\n                      <jats:italic>APOE<\/jats:italic>\n                      -KI) mice (\u03b52\/\u03b52, \u03b53\/\u03b53, and \u03b54\/\u03b54) where the exons in the coding region of\n                      <jats:italic>APOE<\/jats:italic>\n                      are flanked by loxP sites, allowing for cell type-specific manipulation of gene expression. We assessed these mice both alone and after crossing them with mice with amyloid deposition in the brain. Using biochemical and histological methods.\u00a0We also investigated how removal of\n                      <jats:italic>APOE<\/jats:italic>\n                      expression from hepatocytes affected\u00a0cerebral\u00a0amyloid deposition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      As in other\n                      <jats:italic>APOE<\/jats:italic>\n                      knock-in mice, apoE protein was present predominantly in astrocytes in the brain under basal conditions and was also detected in reactive microglia surrounding amyloid plaques. Primary cultured astrocytes and microglia from the\n                      <jats:italic>APOE<\/jats:italic>\n                      -KI mice secreted apoE in lipoprotein particles of distinct size distribution upon native gel analysis with microglial particles being substantially smaller than the HDL-like particles secreted by astrocytes. Crossing of APP\/PS1 transgenic mice to the different\n                      <jats:italic>APOE<\/jats:italic>\n                      -KI mice recapitulated the previously described isoform-specific effect (\u03b54\u2009&gt;\u2009\u03b53) on amyloid plaque and A\u03b2 accumulation. Deletion of\n                      <jats:italic>APOE<\/jats:italic>\n                      in hepatocytes did not alter brain apoE levels but did lead to a marked decrease in plasma apoE levels and changes in plasma lipid profile. Despite these changes in peripheral apoE and on plasma lipids, cerebral accumulation of amyloid plaques in APP\/PS1 mice was not affected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Altogether, these new knock-in strains offer a novel and dynamic tool to study the role of\n                      <jats:italic>APOE<\/jats:italic>\n                      in AD pathogenesis in a spatially and temporally controlled manner.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-019-0337-1","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T07:32:48Z","timestamp":1571297568000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Lack of hepatic apoE does not influence early A\u03b2 deposition: observations from a new APOE knock-in model"],"prefix":"10.1186","volume":"14","author":[{"given":"Tien-Phat V.","family":"Huynh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainsley C.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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