Alzheimer’s disease (AD) is characterized by extracellular amyloid-β (Aβ) deposition, intracellular tau pathology, neuroinflammation, and progressive neurodegeneration. Increasing evidence suggests that chronic peripheral inflammatory conditions may influence the onset and progression of AD. Periodontitis, a dysbiosis-driven inflammatory disease of the tooth-supporting tissues, has emerged as a potential contributor through systemic immune activation, recurrent bacteremia, and dissemination of microbial virulence factors.

This narrative review selectively synthesizes foundational and recent peer-reviewed human observational, neuropathologic, experimental, and interventional studies identified through targeted literature searches and citation chaining; studies were prioritized for direct mechanistic or translational relevance to the oral–brain axis. Epidemiologic studies report associations of periodontal disease with cognitive decline, dementia, and cerebral amyloid burden, whereas experimental work supports biologically plausible pathways involving systemic inflammation, blood–brain barrier dysfunction,
neuroglial activation, amyloid and tau signaling, gingipain-mediated neurotoxicity, oxidative stress, extracellular vesicles, vascular dysfunction, and oral–gut–brain interactions.

Current evidence supports association and biologic plausibility more strongly than causation. No randomized trial has demonstrated that periodontal therapy prevents cognitive decline or AD, and the phase 2/3 GAIN trial of the gingipain inhibitor atuzaginstat did not meet its co-primary cognitive or functional endpoints. Periodontal prevention and treatment should be recommended for their established oral and general-health benefits; whether they alter AD incidence or progression remains unproven.