Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer's disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly , has garnered significant attention. , a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood-brain barrier disruption, neuroinflammation, and neuronal damage. -derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into -mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management.
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College of Biological Sciences, Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Rd E, Guelph, ON, Canada.
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Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China. Electronic address:
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Instituto de Investigación Sanitaria Aragón, 50009 Zaragoza, Spain.
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Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
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Department of Aquatic Animal Disease, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa 16059, Türkiye.
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