{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:12:32Z","timestamp":1788671552371,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M772189"],"award-info":[{"award-number":["2025M772189"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Obesity may increase Alzheimer's disease (AD) risk, yet the underlying mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We investigated this link through global epidemiology, Mendelian randomization (MR), transcriptomics, clinical cohort validation, and mechanistic exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>High body mass index (BMI)\u2013attributable AD disability\u2010adjusted life years and deaths increased 4\u2010fold from 1990\u20132021, with projections indicating a tripling by 2050. MR analyses found that elevated BMI was genetically related to increased AD risk. Haptoglobin (HP) was identified as a core mediator between them. HP expression was correlated with plasma AD biomarkers and cognitive scores. Mechanistically, HP localized to plaque\u2010associated microglia and suppressed microglial amyloid beta (A\u03b2) phagocytosis and DNAX activating protein of 12 kDa (Dap12)\/Spleen tyrosine kinase (Syk) pathway with modulating disease\u2010associated microglial transcriptional programs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>This study identified HP as a strong candidate mediator linking obesity to AD pathogenesis through inhibiting the phagocytosis of A\u03b2 by microglia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71759","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T04:38:11Z","timestamp":1787546291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010omics identification of haptoglobin as a novel target for increased Alzheimer's disease risk associated with obesity through inhibiting the phagocytosis of A\u03b2 by disease\u2010associated microglia"],"prefix":"10.1002","volume":"22","author":[{"given":"Xiaohang","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Medical Center on Aging Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Neurology and Institute of Neurology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Medical Center on Aging Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijing","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Medical Center on Aging Ruijin 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