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Alterations in DNA methylation are increasingly recognized as critical in modulating immune responses and neurodegenerative processes. This review examines the evidence linking periodontal inflammation to AD pathogenesis and evaluates the potential of blood-based epigenetic biomarkers for early diagnosis and risk stratification. A narrative review was conducted by integrating findings from both preclinical and clinical studies that investigated the relationship between periodontitis and AD. Emphasis was placed on research assessing DNA methylation profiles, gene expression alterations, and the impact of proinflammatory mediators on the central nervous system. Particular attention was given to studies examining the role of the immune and complement systems in mediating the effects of chronic oral inflammation. The evidence indicates that chronic periodontal inflammation can trigger systemic responses that compromise the integrity of the blood-brain barrier, thereby facilitating the accumulation of amyloid-\u03b2 plaques and hyperphosphorylated tau proteins in the brain. Aberrant methylation patterns in genes related to immune regulation and protein processing suggest converging molecular pathways between periodontitis and AD. Moreover, emerging data reveal that epigenetic alterations detectable in peripheral blood closely mirror cerebral changes, opening new avenues for early detection. As a narrative review, our synthesis is hypothesis-generating and does not establish causality; the proposed epigenetic link between periodontitis and AD remains provisional pending longitudinal and interventional confirmation.<\/jats:p>","DOI":"10.1177\/13872877251397406","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:03:22Z","timestamp":1764169402000},"page":"499-525","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Relationship periodontitis and Alzheimer's disease: Relevant aspects from an epigenetic view"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8712-3123","authenticated-orcid":false,"given":"Tatiana","family":"Chac\u00f3n","sequence":"first","affiliation":[{"name":"Oral Health Department, Universidad Aut\u00f3noma de Manizales, Manizales, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-6269","authenticated-orcid":false,"given":"Hern\u00e1n","family":"Hern\u00e1ndez-Hincapi\u00e9","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n Salud Integral Bucal - SIB, Research project \u201cEstudio de genes candidatos de marcadores epigen\u00e9ticos de metilaci\u00f3n de ADN en leucocitos perif\u00e9ricos de un grupo de pacientes colombianos con enfermedad de Alzheimer y periodontitis\u201d, Faculty of Dentistry, Health Sciences Division, Universidad Santo Tom\u00e1s, Bucaramanga, Cra. 18 No. 9 - 27, Bucaramanga, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00488-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12237"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2023.11.003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12620"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05940-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00789-z"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0150-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0348-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-00942-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00403-3"},{"key":"e_1_3_2_12_2","first-page":"74","article-title":"Blood samples as a surrogate for brain samples in methylation studies","volume":"5","author":"Bediaga NG","year":"2017","unstructured":"Bediaga NG, Elcoroaristizabal X, Calvo B, et al. 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