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We assessed the impact of the semi\u2010synthetic LXR agonist 22\u2010ketositosterol on disease progression in an AD mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      From 5.5\u2009months of age, APPswePS1\u0394E9 (AD) mice and wild\u2010type (WT) littermates received a regular or 22\u2010ketositosterol\u2010supplemented diet (0.017%\n                      <jats:italic>w<\/jats:italic>\n                      \/\n                      <jats:italic>w<\/jats:italic>\n                      ). Cognition was assessed with object location and recognition tasks and a spontaneous alternation Y\u2010maze test. Amyloid \u03b2 was quantified using immunohistochemistry (IHC) and enzyme\u2010linked immunosorbent assay (ELISA), microglia (Iba1, CD68) and astrocyte (GFAP) markers using IHC. Sterols were determined in food, serum, liver and cerebellum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>22\u2010Ketositosterol activated both liver X receptors\u2010\u03b1 and \u2010\u03b2 and promoted cholesterol efflux in cell cultures. Diet supplementation with 22\u2010ketositosterol prevented a decline in the performance of APPswePS1\u0394E9 mice in the object location task but not in the other two tasks. Without affecting amyloid \u03b2 deposition, 22\u2010ketositosterol decreased microglia (Iba1, CD68) and astrocyte (GFAP) markers in the cortex and hippocampus of APPswePS1\u0394E9, suggesting potential anti\u2010inflammatory effects. No lipid accumulation was detected in the liver or serum upon 22\u2010ketositosterol supplementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Diet supplementation with 22\u2010ketositosterol prevented the decline in spatial memory of APPswePS1\u0394E9 mice. Our data suggest therapeutic benefits of 22\u2010ketositosterol possibly by enhancing cholesterol efflux and mitigating inflammatory responses, without inducing hepatosteatosis or hypertriglyceridemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70031","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T19:36:56Z","timestamp":1744745816000},"page":"3744-3766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role for the liver X receptor agonist 22\u2010ketositosterol in preventing disease progression in an Alzheimer's disease mouse model"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-3379","authenticated-orcid":false,"given":"Nikita","family":"Martens","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section Pharmacology and Vascular Medicine Erasmus University Medical Center  Rotterdam The Netherlands"},{"name":"Department of Neuroscience, Biomedical Research Institute, Faculty of Medicine and Life Sciences Hasselt University  Hasselt Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section Pharmacology and Vascular Medicine Erasmus University Medical Center  Rotterdam The Netherlands"},{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy Ocean University of China  Qingdao China"},{"name":"Institute of Clinical Chemistry and Clinical Pharmacology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sammie C.","family":"Yam","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section Pharmacology and Vascular Medicine Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Food and Drug University of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Pontini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank P. 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