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Soluble epoxide hydrolase (sEH), an enzyme with proinflammatory products, is upregulated in the AD brain. Emerging evidence suggests that AD-related inflammation may reflect systemic metabolic changes, however, peripheral organs remain understudied. Because the liver has a pivotal role in lipid metabolism and bioactive lipid mediator homeostasis, we hypothesized that inflammatory lipid mediator changes in the AD brain may be reflected in, and potentially shaped by, hepatic lipid metabolism.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Paired postmortem brain and liver tissues from 16 cognitively normal and 63 AD donors with median postmortem intervals (PMI) of 3.08 hours were analyzed for free and esterified forms of oxylipins and endocannabinoids. ANCOVA models evaluated effects of AD diagnosis, sex, and AD-by-sex interactions, adjusting for analytical batch, age, body mass index, and PMI.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>AD-associated differences in lipid mediator profiles were observed in both brain and liver, with a broader pattern of differences in liver. Differences involved CYP\/sEH-related metabolites and fatty acid ethanolamides, with several metabolites also showing AD-by-sex interactions. Sex-associated differences were also more pronounced in the liver than the brain.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>These results suggest AD-associated lipid dysregulation across both central and peripheral tissues. The prominent hepatic alterations highlight the liver as an important site of peripheral lipid mediator dysregulation in AD and suggest that hepatic metabolic changes may contribute to or reflect inflammatory lipid remodeling in the brain.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.22.26363708","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:20:19Z","timestamp":1790220019000},"source":"Crossref","is-referenced-by-count":0,"title":["Distinct lipid mediator profiles in brain and liver tissues in Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-4144","authenticated-orcid":false,"given":"Sitong","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pathology and Lab Medicine, University of California Davis Medical Center, Sacramento, CA, USA"},{"name":"Alzheimer\u2019s Disease Research Center, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3637-3450","authenticated-orcid":false,"given":"Kamil","family":"Borkowski","sequence":"additional","affiliation":[{"name":"Genome Center, University of California, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuanyi","family":"Liang","sequence":"additional","affiliation":[{"name":"Genome Center, University of California, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-2011","authenticated-orcid":false,"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of California, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Newman","sequence":"additional","affiliation":[{"name":"Genome Center, University of California, Davis, CA, USA"},{"name":"Department of Nutrition, University of California, Davis, CA, USA"},{"name":"Western Human Nutrition Research Center, United States Department of Agriculture, Agriculture Research Service, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Maezawa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Lab Medicine, University of California Davis Medical Center, Sacramento, CA, USA"},{"name":"Alzheimer\u2019s Disease Research Center, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Way","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Lab Medicine, University of California Davis Medical Center, Sacramento, CA, USA"},{"name":"Alzheimer\u2019s Disease Research Center, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092605100554000_2026.09.22.26363708v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/S13311-020-00854-1"},{"key":"2026092605100554000_2026.09.22.26363708v1.2","doi-asserted-by":"crossref","unstructured":"H.-T. 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