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Chronic oral inflammation caused by PD is accompanied by biological immunological responses, unchecked inflammation, and the spread of periodontal bacteria, all contributing to nervous system inflammation and\n                    <jats:sc>AD<\/jats:sc>\n                    pathogenesis. There are two primary pathways: (a) Inflammatory cascades, in which pro\u2010inflammatory cytokines, such as IL\u20101\u03b2 and TNF\u2010\u03b1, originating from periodontal lesions, cause inflammation in the brain region of the head, resulting in tau hyperphosphorylation, amyloid beta (A\u03b2) accumulation, and disruption of the blood\u2013brain barrier; (b) Microbial involvement, in which oral pathogens, such as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Porphyromonas\u2009gingivalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P.\u2009gingivalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    ), can enter the bloodstream, enter the trigeminal nerve, and activate microglia. The fact that\n                    <jats:sc>AD<\/jats:sc>\n                    patients are known to experience greater periodontal disease than others, together with additional research maintaining the connection between oral dysbiosis and neurodegeneration, further supports these pathways. In older patients, the collapse of the blood\u2013brain barrier exacerbates inhibitor breaches, allowing poisons and microorganisms to enter, increasing the formation of A\u03b2 and neurotoxicity. Conversely, periodontal infections may exacerbate\n                    <jats:sc>AD<\/jats:sc>\n                    over time by causing a loss in peri\u2010oral neglect (cognitive decline) and self\u2010oral care (hygiene). To clarify the directed causative links that therapeutic approaches seek to resolve, rather than an attributable association, systematic reviews help interdisciplinary approaches focus on the integral integration of oral healthcare into\n                    <jats:sc>AD<\/jats:sc>\n                    preventive policies built around proactive\n                    <jats:sc>AD<\/jats:sc>\n                    management systems and longitudinal research studies. This evidence synthesis sets the oral\u2013brain interaction as an axis of critically heightened focus for investigating\n                    <jats:sc>AD<\/jats:sc>\n                    pathogenesis, maximally shifting the paradigm for proactive intervention and tailored care models.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70366","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T11:03:51Z","timestamp":1766142231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pathophysiological Insights Into the Oral\u2013Brain Axis: Evidence\u2010Based Mechanisms Connecting Periodontitis and Alzheimer's Disease"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7951-9231","authenticated-orcid":false,"given":"Mohamed\u00a0Abd\u00a0Elsattar","family":"Ahmed","sequence":"first","affiliation":[{"name":"Oral Medicine and Periodontology Department, Faculty of Dental Medicine King Salman International University  El Tor South Sinai Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelnaser\u00a0Hussein","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Faculty of Oral and Dental Medicine and Surgery Sinai University  Arish North Sinai Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nourhan\u00a0Hamed","family":"Elmoghazy","sequence":"additional","affiliation":[{"name":"Faculty of Oral and Dental Medicine and Surgery Sinai University  Arish North Sinai Egypt"},{"name":"Department of Oral Biology, Faculty of Dentistry The British University in Egypt  El Sherouk City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr\u00a0Abdelsalam","family":"Shaheraldin","sequence":"additional","affiliation":[{"name":"Immunology and Biotechnology Division, Zoology Department, Faculty of Science Tanta University  Tanta Egypt"},{"name":"Center of Excellence in Cancer Research, New Tanta University Teaching Hospital Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Ghalwash","sequence":"additional","affiliation":[{"name":"Oral Medicine and Periodontology, Faculty of Dentistry The British University in Egypt  El Sherouk City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.4172\/2314\u20107326.1000200"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13038"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/dj12100331"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00235"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010200064"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010020\u20100736\u20102"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010150652"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.46311"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2018.12.001"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13861"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010160212"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010017\u20100282\u20106"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.15828"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jds.2024.04.002"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25052612"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics17020141"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784\u2010020\u201003489\u2010w"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.647734"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903\u2010024\u201005409\u2010w"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.080474"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084509"},{"key":"e_1_2_15_25_1","unstructured":"Farhad S. 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