March 3, 2026CNS Neuroscience & Therapeutics2 citationsOpen Access

The Interface of Oral and Brain Health: Current Insights Into the Bidirectional Relationship Between Alzheimer's Disease and Periodontitis

WZWeidong ZhangBinzhou University SLShasha LiBinzhou People's Hospital YCYajun CuiShandong University

Key Points

Periodontitis is linked to increased risk of Alzheimer's Disease, and cognition decline complicates oral hygiene habits, worsening both conditions.
Key evidence shows that periodontal pathogens like Porphyromonas gingivalis can induce neuroinflammation and promote β-amyloid aggregation in the brain.
Analysis of mechanisms reveals how AD disrupts bone homeostasis, with Aβ activating osteoclasts through RAGE/NF-κB signaling, worsening periodontitis.
This highlights the need for longitudinal studies and therapeutic interventions targeting the oral-brain axis to prevent disease progression.

Abstract

Epidemiologically, periodontitis is associated with an increased risk of AD, while AD patients exhibit a higher prevalence of periodontitis, driven by cognitive decline-impaired oral hygiene and synergistic inflammatory mechanisms. Pathologically, periodontal pathogens (e.g., Porphyromonas gingivalis) translocate to the brain via hematogenous, trigeminal, or oral-intestinal pathways, inducing neuroinflammation, β-amyloid (Aβ) aggregation, and tau hyperphosphorylation through virulence factors like gingipains and LPS. Conversely, AD-related neurodegeneration disrupts bone homeostasis to aggravate periodontitis via multiple mechanisms: (1) Aβ-mediated osteoclast activation through RAGE/NF-κB signaling and suppression of osteoblastogenesis; (2) autonomic nervous system dysregulation, where sympathetic hyperactivity promotes RANKL-dependent bone resorption; and (3) endocrine dysfunction, including HPA axis hyperactivation (chronic hypercortisolism), sex hormone deficiency, insulin resistance, and growth hormone/IGF-1 insufficiency, all of which perturb the balance between bone formation and resorption. Aging exacerbates this bidirectional interplay through immunosenescence (e.g., impaired neutrophil phagocytosis, senescent microglia) and inflammaging, creating a pro-degenerative milieu that amplifies both diseases. Clinical interventions, such as periodontal therapy and microbiota modulation, show promise in reducing systemic inflammation and slowing AD progression, though causal links require validation. Future research must prioritize longitudinal cohort studies, pathogen-specific mechanistic investigations, and translational strategies targeting the oral-brain axis to develop preventive interventions for aging populations.

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