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Chronic periodontitis has emerged as a modifiable risk factor, and extracellular vesicles (EVs) have recently been proposed as important mediators of the periodontal\u2013brain axis. Periodontal pathogens such as\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    (\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    ) release bacterial EVs enriched with virulence factors including gingipains, lipopolysaccharide, and regulatory RNAs. These vesicles can enter systemic circulation, interact with the blood\u2013brain barrier, activate microglia, and trigger inflammatory signaling pathways such as NF-\u03baB and NLRP3. These processes contribute to neuroinflammation, amyloid-\u03b2 accumulation, and tau hyperphosphorylation, hallmarks of AD pathology. Host-derived EVs further contribute to this complex signaling network by facilitating intercellular communication and potentially propagating pathogenic proteins while also carrying protective molecules. Preclinical studies suggest that periodontal-derived vesicles can reach the hippocampus and impair cognition, while clinical studies have detected\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    DNA and gingipains in AD brain tissues. EV\u2013associated biomarkers in blood or cerebrospinal fluid and engineered therapeutic vesicles represent promising tools for early diagnosis and intervention. Targeting oral microbial EVs may therefore offer novel avenues for AD prevention and therapy.\n                  <\/jats:p>","DOI":"10.1007\/s12640-026-00802-5","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:11:38Z","timestamp":1784189498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Microbial Extracellular Vesicles as Novel Mediators of Alzheimer\u2019s Pathogenesis: A Critical Review of the Periodontal\u2013Brain Axis"],"prefix":"10.1007","volume":"44","author":[{"given":"Seyed Ebrahim","family":"Alavi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Ebrahimi Shahmabadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Love","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun V.","family":"Kurumathur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavanya A.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"4","key":"802_CR1","doi-asserted-by":"publisher","first-page":"5967","DOI":"10.1096\/fj.202000034r","volume":"34","author":"EL Abner","year":"2020","unstructured":"Abner EL, Elahi FM, Jicha GA, Mustapic M, Al-Janabi O, Kramer JH, Kapogiannis D, Goetzl EJ (2020) Endothelial\u2010derived plasma exosome proteins in Alzheimer\u2019s disease angiopathy. 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