{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:02:33Z","timestamp":1790784153768,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Metabolic stress increases Alzheimer's disease (AD) risk, but mechanisms linking metabolic dysfunction to neuroimmune dysregulation remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We assessed cognition in community\u2010dwelling participants and used high\u2010fat diet (HFD)\u2010fed 5xFAD mice, high glucose and high palmitate (HGHP)\u2010treated regulatory T cell (Treg) co\u2010cultures, and adoptive Treg transfer to evaluate metabolic stress\u2010associated neuroimmune dysfunction. Flow cytometry, RNA sequencing, positron emission tomography computed tomography, and electrophysiology assessed Treg function, AD pathology, cerebral metabolism, and synaptic plasticity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Metabolic stress impaired Treg stability and function, accompanied by increased Z\u2010DNA\u2010binding protein 1 (ZBP1) expression and activation of apoptotic and necroptotic signaling. Treg dysfunction was associated with enhanced glial activation and neuronal injury. Under HGHP stress, ZBP1\u2010deficient Tregs showed improved survival and stronger immunosuppressive activity, more effectively limiting glial activation and preserving neuronal integrity. In vivo, ZBP1\u2010deficient Treg transfer conferred greater neuroprotection than wild\u2010type Treg transfer in HFD\u2010fed AD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>ZBP1 may contribute to metabolic stress\u2013induced Treg dysfunction and represent a candidate target to improve Treg\u2010based therapy in HFD\u2010fed AD mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71896","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:13:41Z","timestamp":1790781221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZBP1\u2010mediated Treg cell dysfunction exacerbates neuroimmune dysregulation in Alzheimer's disease under metabolic 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Huashan Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqiu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Changzheng Hospital Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzheng","family":"Chen","sequence":"additional","affiliation":[{"name":"MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Translational Neuroscience Jing'an District Centre Hospital of Shanghai Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics National Clinical Research Center 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