{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:44:11Z","timestamp":1788381851780,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Late\u2010onset Alzheimer's disease (LOAD) is a complex neurodegenerative disease characterized by multiple progressive stages, glucose metabolic dysregulation, Alzheimer's disease (AD) pathology, and inexorable cognitive decline. Discovery of metabolic profiles unique to sex, apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) genotype, and stage of disease progression could provide critical insights for personalized LOAD medicine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sex\u2010 and\n                      <jats:italic>APOE<\/jats:italic>\n                      \u2010specific metabolic networks were constructed based on changes in 127 metabolites of 656 serum samples from the Alzheimer's Disease Neuroimaging Initiative cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Application of an advanced analytical platform identified metabolic drivers and signatures clustered with sex and\/or\n                      <jats:italic>APOE<\/jats:italic>\n                      \u025b4, establishing patient\u2010specific biomarkers predictive of disease state that significantly associated with cognitive function. Presence of the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u025b4 shifts metabolic signatures to a phosphatidylcholine\u2010focused profile overriding sex\u2010specific differences in serum metabolites of AD patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide an initial but critical step in developing a diagnostic platform for personalized medicine by integrating metabolomic profiling and cognitive assessments to identify targeted precision therapeutics for AD patient subgroups through computational network modeling.<\/jats:p>\n                  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