{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:25:40Z","timestamp":1777397140398,"version":"3.51.4"},"reference-count":56,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institute of Aging","award":["R01AG080773"],"award-info":[{"award-number":["R01AG080773"]}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["T32 DK007646"],"award-info":[{"award-number":["T32 DK007646"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018378","name":"Owens Family Foundation","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100018378","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rick Sharp Alzheimer's Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lipids synthesized in astrocytes are distributed to other brain cells in high-density lipoprotein-like ApoE particles. ApoE, which is a powerful genetic risk factor for developing Alzheimer's disease, is secreted differently depending on genotype. Secretion of ApoE from mouse astrocytes is regulated by the mevalonate pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to understand if the regulation of ApoE secretion from astrocytes by the mevalonate pathway was the same between mouse ApoE and ApoE from humanized mice, and if this is impacted by ApoE isoform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Astrocyte-enriched glial cultures from wild-type and humanized ApoE targeted-replacement mice were treated with pharmacological inhibitors of various steps along the mevalonate pathway and ApoE in the conditioned media was measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that statins and prenylation inhibitors, but not specific cholesterol inhibitors, reduce extracellular ApoE lipoparticle levels in astrocyte-enriched glial cultures, and that this occurs in cells harboring either the mouse ApoE or any of the three human ApoE genotypes to a similar extent. We find that geranylgeranylation modulates ApoE release from astrocytes, and it does so independent of ApoE genotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results suggest that prenylation broadly regulates ApoE secretion from astrocytes regardless of ApoE genotype, and that this is mediated specifically by geranylgeranylation. Therefore, our data implicates geranylgeranylation as a general mechanism modulating ApoE release from astrocytes, but likely is not responsible for the reported baseline differences in ApoE secretion seen in vivo and in vitro across genotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251317732","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T01:20:27Z","timestamp":1740446427000},"page":"473-487","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of glial ApoE secretion by the mevalonate pathway is independent of ApoE isoform"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5416-7795","authenticated-orcid":false,"given":"Joshua L","family":"Milstein","sequence":"first","affiliation":[{"name":"Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA, USA"},{"name":"Department of Neuroscience, University of Virginia, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8055-1894","authenticated-orcid":false,"given":"Joshua A","family":"Kulas","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA, USA"},{"name":"Department of Neuroscience, University of Virginia, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7420-3795","authenticated-orcid":false,"given":"Aria","family":"Kamal","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA, USA"},{"name":"Department of Neuroscience, University of Virginia, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1453-9456","authenticated-orcid":false,"given":"An B","family":"Lo","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA, USA"},{"name":"Department of Neuroscience, University of Virginia, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-3447","authenticated-orcid":false,"given":"Heather A","family":"Ferris","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA, USA"},{"name":"Department of Neuroscience, University of Virginia, Charlottesville, VA, USA"},{"name":"Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-180"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0419"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14279-8"},{"key":"e_1_3_5_6_2","doi-asserted-by":"crossref","unstructured":"Feringa FM Hertog SJK Wang L et al. 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