{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:09:43Z","timestamp":1788775783741,"version":"build-2803163510"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005922","name":"International Association for Dental Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005922","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dent. Med."],"abstract":"<jats:p>\n                    Down Syndrome (DS) involves widespread systemic issues, including a near-universal development of early-onset Alzheimer's Disease, driven by factors beyond Amyloid Precursor Protein (APP) over-expression, such as chronic neuroinflammation and endosomal dysfunction. High prevalence of periodontitis in this population acts as a significant source of peripheral inflammation that may accelerate this cognitive decline, necessitating further study into the bidirectional, pro-inflammatory links between systemic health and neurodegeneration in DS. This review analyzes the common pathophysiological pathways linking periodontitis and AD development within the DS population, evaluating how oral dysbiosis acts as a systemic driver of neurodegeneration. We synthesized current molecular, microbiological, and clinical evidence evaluating the bidirectional relationships between trisomy 21-induced immune dysfunction, severe periodontitis, and accelerated cognitive decline. Individuals with DS exhibit a heightened susceptibility to aggressive, early-onset periodontitis starting as early as age six. This chronic oral dysbiosis facilitates microbial translocation, allowing periodontal pathogens (e.g.,\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    ) and their virulence factors to cross the blood-brain barrier via circulatory or trigeminal routes. In the central nervous system, these pathogens encounter microglial populations already genetically primed by trisomy 21. This induces an exacerbated M1 microglial phenotype response, triggering sustained neuroinflammation, defensive over-deposition of Amyloid-\u03b2 (A\u03b2) plaques, and upregulation of GSK-3\u03b2, which accelerates Tau protein hyperphosphorylation. While bidirectional links are strongly indicated, current literature lacks robust longitudinal studies connecting periodontal, microbiological, and cognitive data to establish definitive causality. Early clinical intervention and management of gum disease present a critical therapeutic window to delay the onset and slow the progression of AD in this vulnerable population.\n                  <\/jats:p>","DOI":"10.3389\/fdmed.2026.1930049","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:33:00Z","timestamp":1788773580000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Periodontitis and Alzheimer's disease, common pathways in down syndrome"],"prefix":"10.3389","volume":"7","author":[{"given":"Fabio","family":"Arriola-Pacheco","sequence":"first","affiliation":[{"name":"Faculty of Dentistry, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia Leonor","family":"Pinz\u00f3n-T\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Universidad Aut\u00f3noma de Yucat\u00e1n M\u00e9rida","place":["Merida, Yucat\u00e1n, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Serrano-Pi\u00f1a","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Universidad Aut\u00f3noma de Yucat\u00e1n M\u00e9rida","place":["Merida, Yucat\u00e1n, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertha Arelly","family":"Carrillo-\u00c1vila","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Universidad Aut\u00f3noma de Yucat\u00e1n M\u00e9rida","place":["Merida, Yucat\u00e1n, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"D\u00edaz-Z\u00fa\u00f1iga","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universidad de Atacama","place":["Copiap\u00f3, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Melgar-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Conservative Dentistry Department, Faculty of Dentistry, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor Manuel","family":"Mart\u00ednez-Aguilar","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Universidad Aut\u00f3noma de Yucat\u00e1n M\u00e9rida","place":["Merida, Yucat\u00e1n, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12929-015-0138-y","article-title":"Down syndrome: an insight of the disease","volume":"22","author":"Asim","year":"2015","journal-title":"J Biomed 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