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This signature also emerges in patient\u2010derived cortical organoids prior to amyloid beta and tau pathology, supporting a genotype\u2010driven mechanism. Cross\u2010tissue comparisons reveal shared innate and antiviral responses alongside tissue\u2010specific immune signaling. Notably, a 12\u2010week medical ketogenic diet partially reversed the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 immune signature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      These findings position immune dysregulation as an early and tractable driver of AD risk in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers with direct implications for targeted prevention strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71714","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:11:27Z","timestamp":1788181887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross\u2010tissue immune profiling of\n                    <i>APOE<\/i>\n                    \u03b54 reveals early dysregulation in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Artur","family":"Shvetcov","sequence":"first","affiliation":[{"name":"Neurodegeneration and Disease Modelling Laboratory Westmead Institute for Medical Research, The University of Sydney  Westmead New South Wales Australia"},{"name":"School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Thomson","sequence":"additional","affiliation":[{"name":"Neurodegeneration and Disease Modelling Laboratory Westmead Institute for Medical Research, The University of Sydney  Westmead New South Wales Australia"},{"name":"School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales 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