{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:27:12Z","timestamp":1786976832558,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Periodontal pathogen\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      is epidemiologically linked to Alzheimer's disease (AD), yet how oral infection disrupts the central circadian clock to drive hippocampal neurodegeneration remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      C57BL\/6 mice received oral\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      for 6 months; hippocampal clock gene oscillations, phosphorylated protein kinase B (p\u2010AKT), glial fibrillary acidic protein (GFAP)\/Ionized calcium\u2010binding adapter molecule 1 (Iba1), and amyloid beta (A\u03b2) load were quantified. C8\u2010D1A astrocytes and BV2 microglia were infected with\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      \u00a0\u00b1\u00a0phosphatidylinositol 3\u2010kinase\/protein kinase B (PI3K\/AKT inhibitor or agonist;\n                      <jats:italic>Bmal1<\/jats:italic>\n                      (brain and muscle ARNT\u2010like 1)\/\n                      <jats:italic>Clock<\/jats:italic>\n                      (circadian locomotor output cycles kaput) were knocked down by lentivirus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      \u2010induced periodontitis dampened hippocampal\n                      <jats:italic>Bmal1<\/jats:italic>\n                      rhythms, lowered p\u2010AKT, activated glia, and elevated A\u03b2 and interleukin 1\u03b2 (IL\u20101\u03b2). In glial cells,\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      flattened\n                      <jats:italic>Bmal1<\/jats:italic>\n                      oscillation; PI3K blockade mimicked these effects, whereas AKT agonist restored rhythms and suppressed GFAP\/Iba1\/IL\u20101\u03b2.\n                      <jats:italic>Bmal1<\/jats:italic>\n                      knockdown alone triggered glial activation and cytokine release.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      oral infection suppresses PI3K\/AKT signaling, destabilizing glial circadian clocks and unleashing neuroinflammation that fosters hippocampal AD\u2010like pathology; rescuing PI3K\/AKT or clock function may mitigate the oral\u2013brain axis in AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71543","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T03:38:06Z","timestamp":1781149086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>Porphyromonas gingivalis<\/i>\n                    disrupts hippocampal circadian clock via PI3K\/AKT pathway, exacerbating Alzheimer\u2010like pathology"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0228-7052","authenticated-orcid":false,"given":"Chunmei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Geriatric Dentistry, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan 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National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Geriatric Dentistry, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Geriatric Dentistry, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Geriatric Dentistry, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan 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