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We express here the human APOE isoforms in astrocytes in an\n Apoe<\/jats:italic>\n -deficient AD mouse model. This is not only sufficient to restore the amyloid plaque pathology but also induces the characteristic transcriptional pathological responses in\n Apoe-<\/jats:italic>\n deficient microglia surrounding the plaques. We find that both APOE4 and the protective APOE2 from astrocytes increase fibrillar plaque deposition, but differentially affect soluble A\u03b2 aggregates. Microglia and astrocytes show specific alterations in function of\n APOE<\/jats:italic>\n genotype expressed in astrocytes. Our experiments indicate a central role of the astrocytes in APOE mediated amyloid plaque pathology and in the induction of associated microglia responses.\n <\/jats:p>","DOI":"10.1038\/s44321-024-00162-7","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T09:14:24Z","timestamp":1731316464000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["APOE from astrocytes restores Alzheimer\u2019s A\u03b2-pathology and DAM-like responses in APOE deficient microglia"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7282-2615","authenticated-orcid":false,"given":"Pranav","family":"Preman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-9778","authenticated-orcid":false,"given":"Daan","family":"Moechars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-5806","authenticated-orcid":false,"given":"Emre","family":"Fertan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"Wolfs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutgarde","family":"Serneels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Disha","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Lamote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Poovathingal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Snellinx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Mancuso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-0577","authenticated-orcid":false,"given":"Sriram","family":"Balusu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Klenerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-7870","authenticated-orcid":false,"given":"Amaia M","family":"Arranz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5694-2409","authenticated-orcid":false,"given":"Mark","family":"Fiers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5455-5819","authenticated-orcid":false,"given":"Bart","family":"De Strooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"162_CR1","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1073\/pnas.0812697106","volume":"106","author":"F Agosta","year":"2009","unstructured":"Agosta F, Vossel KA, Miller BL, Migliaccio R, Bonasera SJ, Filippi M, Boxer AL, Karydas A, Possin KL, Gorno-Tempini ML (2009) Apolipoprotein E \u03b54 is associated with disease-specific effects on brain atrophy in Alzheimer\u2019s disease and frontotemporal dementia. 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