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Whether apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) \u03b54 modifies associations of baseline AST\/ALT with longitudinal Alzheimer's disease (AD) trajectories is unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In 2709 Alzheimer's Disease Neuroimaging Initiative participants, linear mixed\u2010effects models estimated AST\/ALT\u2010associated longitudinal change in Mini\u2010Mental State Examination, Alzheimer's Disease Assessment Scale 13\u2010item Cognitive subscale, and AD\u2010signature cortical thickness; Cox models evaluated continuous AST\/ALT and an extreme\u2010tertile\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 \u00d7 AST\/ALT comparison for clinical progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Higher baseline AST\/ALT was associated with faster cognitive decline and AD\u2010signature cortical thinning, with larger associations among\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers (interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0006\u20130.040). In clinical\u2010progression analyses, continuous AST\/ALT was not significantly associated with risk (hazard ratio [HR] 1.07 per standard deviation,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.12). In the extreme\u2010tertile comparison,\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers with high AST\/ALT had the highest adjusted hazard (HR 3.08, 95% confidence interval 2.18\u20134.34), but multiplicative and additive interactions were null and incremental discrimination was minimal (\u0394\n                      <jats:italic>C\u00a0=<\/jats:italic>\n                      \u00a0+0.003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Baseline AST\/ALT was associated with faster cognitive and cortical decline, particularly among\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers, but provided limited incremental information for clinical progression beyond\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 and baseline diagnosis. These findings represent a large longitudinal extension of prior liver\u2010enzyme observations and require external validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dad2.70484","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T02:51:26Z","timestamp":1789354286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AST\/ALT,\n                    <i>APOE<\/i>\n                    \u03b54, and Alzheimer's disease progression: A longitudinal cohort study"],"prefix":"10.1002","volume":"18","author":[{"given":"Young Hyeon","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Soonchunhyang University Cheonan Hospital  Cheonan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan\u2010Mo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry 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