The Oral-Brain Axis in Alzheimer's Disease: From Microbial Dysbiosis to Neurodegeneration.

Alzheimer's disease (AD), the most prevalent form of dementia, still lacks a clearly defined pathogenesis and effective disease-modifying therapies, prompting growing interest in peripheral drivers of neurodegeneration. Among these, chronic oral dysbiosis has emerged as a potential risk factor. Disruption of the oral ecosystem in periodontitis promotes systemic inflammation and the circulation of bacterial products capable of influencing brain homeostasis. By integrating molecular findings with epidemiological data linking periodontitis, tooth loss, and poor oral health to increased AD risk, this review examines how oral dysbiosis contributes to systemic inflammation as part of a broader network of interacting factors involved in AD pathophysiology. It describes how inflammatory, gut-microbial, genetic, and barrier-related processes intersect with oral dysbiosis and jointly contribute to the acceleration of AD progression. Building on this systemic perspective, the review highlights emerging oral biomarkers and oral-gut microbiota-targeted therapies as potential tools to address current gaps in early diagnosis and intervention. Overall, this work advances current understanding by integrating previously fragmented evidence and highlighting the key conceptual and methodological gaps that must be addressed to clarify causality and to guide the development of preventive and therapeutic approaches targeting oral health in the context of AD.