Relationship periodontitis and Alzheimer's disease: Relevant aspects from an epigenetic view

Abstract

Periodontitis and Alzheimer's disease (AD) are chronic disorders that share an underlying inflammatory component and emerging epigenetic mechanisms influencing disease progression. 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-β 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.