{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:01:15Z","timestamp":1789624875772,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K21714"],"award-info":[{"award-number":["20K21714"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K23030"],"award-info":[{"award-number":["20K23030"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      (\n                      <jats:italic>Pg<\/jats:italic>\n                      ) is thought to be involved in the progression of Alzheimer's disease (AD). Whether\n                      <jats:italic>Pg<\/jats:italic>\n                      or its contents can reach the brain and directly affect neuropathology is, however, unknown. Here, we investigated whether outer membrane vesicles (OMVs) of\n                      <jats:italic>Pg<\/jats:italic>\n                      translocate to the brain and induce the pathogenic features of AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs were injected into the abdominal cavity of mice for 12\u2009weeks.\n                      <jats:italic>Pg<\/jats:italic>\n                      OMV translocation to the brain was detected by immunohistochemistry using an anti\u2010gingipain antibody. Tau protein and microglial activation in the mouse brain were examined by western blotting and immunohistochemistry. The effect of gingipains on inflammation was assessed by real\u2010time polymerase chain reaction using human microglial HMC3 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Gingipains were detected in the region around cerebral ventricles, choroid plexus, and ventricular ependymal cells in\n                      <jats:italic>Pg<\/jats:italic>\n                      OMV\u2010administered mice. Tau and phosphorylated Tau protein increased and microglia were activated.\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs also increased the gene expression of proinflammatory cytokines in HMC3 cells in a gingipain\u2010dependent manner.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs, including gingipains, can reach the cerebral ventricle and induce neuroinflammation by activating microglia.\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs may provide a better understanding of the implications of periodontal diseases in neurodegenerative conditions such as AD.\n                    <\/jats:p>\n                  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