Impact of Oral Immunity on Neuroinflammation and Neurodegenerative Diseases Publisher



Ashford M ; Ziaei H ; Rezaei N
Source: Advances in Experimental Medicine and Biology Published:2026

Abstract

Oral health is increasingly recognized as an important factor in the regulation of systemic immune responses and neurological health. Disruption of immune homeostasis in oral tissues, particularly in chronic conditions such as periodontitis, has been linked to the development and progression of neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). This chapter explores how chronic inflammatory conditions in the oral cavity, oral dysbiosis, and the presence of specific periodontopathogens contribute to systemic immune activation, microglial priming, and blood–brain barrier dysfunction. The discussion addresses multiple mechanistic pathways underlying these relationships, such as hematogenous spread of microbial components with subsequent systemic immune stimulation, neural signaling via trigeminal and vagal pathways, and alterations in gut-brain communication through the integrated oral–gut–brain axis. The chapter also reviews findings from clinical and experimental studies demonstrating correlations between oral inflammation and cognitive impairment, structural brain alterations, and elevated inflammatory and neurodegenerative biomarkers. Oral health disturbances are considered not only as secondary outcomes of neurological disease but also as a potential contributing factor in their pathogenesis. The emphasis is on the importance of incorporating oral health assessment and maintenance into preventive and therapeutic strategies for neurodegenerative conditions, while highlighting the necessity for well-designed mechanistic investigations to further explain these complex relationships. © 2025 Elsevier B.V., All rights reserved.