{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T09:24:39Z","timestamp":1772789079239,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["(2021GGB016) (2022GGA041) (2023QNA068)\uff082021GGB016\uff09\uff082022GGA041\uff09\uff082023QNA068\uff09"],"award-info":[{"award-number":["(2021GGB016) (2022GGA041) (2023QNA068)\uff082021GGB016\uff09\uff082022GGA041\uff09\uff082023QNA068\uff09"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Periodontitis has been epidemiologically linked to an increased risk of Alzheimer\u2019s disease (AD), yet the mechanistic contribution of periodontal pathogens remains insufficiently understood. Building on our previous findings that\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      outer membrane vesicles (OMVs) induce cardiovascular dysfunction, this study investigates whether these vesicles also drive AD\u2010related pathology using the zebrafish model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We microinjected\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      OMVs into the common cardinal vein of zebrafish larvae to evaluate locomotor behavior, brain injury, and neuroinflammatory responses. Integrated proteomic and transcriptomic analyses were performed to identify alterations in AD\u2010associated pathways, and acetylcholinesterase activity along with A\u03b21\u201342 plaque accumulation were quantified to validate hallmark AD phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>OMV exposure resulted in significant neurotoxicity, locomotor deficits, and robust neuroinflammation, accompanied by pronounced dysregulation of AD-related molecular pathways. Notably, OMVs markedly increased acetylcholinesterase activity and promoted A\u03b21\u201342 deposition in larval brains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      OMVs act as potent inducers of neuronal damage and AD-like pathological features\n                      <jats:italic>in vivo<\/jats:italic>\n                      , providing mechanistic insight into how periodontal pathogens may contribute to neurodegenerative disease progression.\n                    <\/jats:p>\n                  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