Pathophysiological Insights Into the Oral–Brain Axis: Evidence‐Based Mechanisms Connecting Periodontitis and Alzheimer's Disease
Document Type
Article
Publication Date
2025
Abstract
The bidirectional association between Alzheimer's disease (AD) and periodontitis (PD) has been recently demonstrated, indicat-ing how the oral–brain axis connects the two conditions. Chronic oral inflammation caused by PD is accompanied by biologicalimmunological responses, unchecked inflammation, and the spread of periodontal bacteria, all contributing to nervous systeminflammation and AD pathogenesis. There are two primary pathways: (a) Inflammatory cascades, in which pro-inflammatorycytokines, such as IL-1β and TNF-α, originating from periodontal lesions, cause inflammation in the brain region of the head,resulting in tau hyperphosphorylation, amyloid beta (Aβ) accumulation, and disruption of the blood–brain barrier; (b) Microbialinvolvement, in which oral pathogens, such as Porphyromonas gingivalis (P. gingivalis), can enter the bloodstream, enter thetrigeminal nerve, and activate microglia. The fact that AD patients are known to experience greater periodontal disease thanothers, together with additional research maintaining the connection between oral dysbiosis and neurodegeneration, furthersupports these pathways. In older patients, the collapse of the blood–brain barrier exacerbates inhibitor breaches, allowing poi-sons and microorganisms to enter, increasing the formation of Aβ and neurotoxicity. Conversely, periodontal infections mayexacerbate AD over time by causing a loss in peri-oral neglect (cognitive decline) and self-oral care (hygiene). To clarify thedirected causative links that therapeutic approaches seek to resolve, rather than an attributable association, systematic reviewshelp interdisciplinary approaches focus on the integral integration of oral healthcare into AD preventive policies built aroundproactive AD management systems and longitudinal research studies. This evidence synthesis sets the oral–brain interaction asan axis of critically heightened focus for investigating AD pathogenesis, maximally shifting the paradigm for proactive interven-tion and tailored care models (PDF) Pathophysiological Insights Into the Oral–Brain Axis: Evidence‐Based Mechanisms Connecting Periodontitis and Alzheimer's Disease.
Recommended Citation
Ghalwash, Dalia; Abd Elsattar, Mohamed; Hussein, Abdelnaser; Elmoghazy, Nourhan; and Shaheraldin, Amr, "Pathophysiological Insights Into the Oral–Brain Axis: Evidence‐Based Mechanisms Connecting Periodontitis and Alzheimer's Disease" (2025). Dentistry. 495.
https://buescholar.bue.edu.eg/dentistry/495