{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:31:54Z","timestamp":1793298714469,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U54 AG054345"],"award-info":[{"award-number":["U54 AG054345"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We investigated differences in serum and brain metabolites between the early\u2010onset 5XFAD and late\u2010onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL\/6J controls at 6 months of age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We identified sex differences for several classes of metabolites, such as glycerophospholipids, sphingolipids, and amino acids. Metabolic signatures were notably different between brain and serum in both mouse models. The 5XFAD mice exhibited stronger differences in brain metabolites, whereas LOAD1 mice showed more pronounced differences in serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Several of our findings were consistent with results in humans, showing glycerophospholipids reduction in serum of apolipoprotein E (apoE) \u03b54 carriers and replicating the serum metabolic imprint of the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 genotype. Our work thus represents a significant step toward translating metabolic dysregulation from model organisms to human AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This was a metabolomic assessment of two mouse models relevant to Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Mouse models exhibit broad sex\u2010specific metabolic differences, similar to human study cohorts.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The early\u2010onset 5XFAD mouse model primarily alters brain metabolites while the late\u2010onset LOAD1 model primarily changes serum metabolites.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Apolipoprotein E (apoE) \u03b54 mice recapitulate glycerophospolipid signatures of human\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b54 carriers in both brain and serum.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13851","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T12:38:51Z","timestamp":1714221531000},"page":"3987-4001","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Metabolomics profiling reveals distinct, sex\u2010specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Ravi S.","family":"Pandey","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University  Durham North Carolina USA"},{"name":"Institute of Computational Biology Helmholtz Zentrum M\u00fcnchen German Research Center for Environmental Health, Ingolst\u00e4dter Landstra\u00dfe 1  Oberschlei\u00dfheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute for Computational Biomedicine Englander Institute for Precision Medicine Weill Cornell Medicine  New York New York 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