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Methionine restriction (MR) induces the hepatokine FGF21 and may protect brain function, but its efficacy and mechanisms when started late are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Fourteen\u2010month\u2010old male APP\/PS1 mice received 17\u00a0weeks of MR (0.17% methionine); behavioral, histological, and molecular assays were performed and hippocampal FGFR1 was knocked down by adeno\u2010associated virus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Late\u2010life MR improved peripheral glucose\/lipid profiles, reduced A\u03b2 deposition, preserved synaptic markers, and suppressed neuroinflammation. MR\u2010induced hepatic FGF21 and brain FGFR1\u2010AMPK\u03b1 signaling to inhibit NF\u03baB; hippocampal FGFR1 knockdown abolished MR's neuroprotective effects while leaving peripheral metabolic changes intact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Even when initiated in late life, MR robustly reduces AD pathology via the hepatic FGF21\u2010brain FGFR1 axis, independent of peripheral metabolic changes. These preclinical findings position MR and FGF21\u2010FGFR1 axis as actionable late\u2010life intervention targets with potential for clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71287","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T10:31:29Z","timestamp":1773484289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Late\u2010life methionine restriction attenuates neuroinflammation in Alzheimer's disease mice via FGF21 activation in a metabolism\u2010independent manner"],"prefix":"10.1002","volume":"22","author":[{"given":"Yuyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratory of Functional Chemistry and Nutrition of Food College of Food Science and Engineering Northwest A&amp;F University  Yangling Shaanxi 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