Affiliations: [a] Oral & Dental Sciences Research Group, School of Medicine and Dentistry, University of Central Lancashire, Preston, UK | [b] Specialist in Special Care Dentistry, University of Central Lancashire, Preston, UK | [c] School of Forensic and Investigative Sciences, University of Central Lancashire, Preston, UK | [d] School of Psychology, University of Central Lancashire, Preston, UK | [e] Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA
Correspondence:
[*]
Correspondence to: Dr. Sim K. Singhrao, Oral & Dental Sciences Research Group, School of Medicine and Dentistry, University of Central Lancashire, Preston, UK. Tel.: +44 1772 895137; Fax: +44 1772 892965; E-mail: SKSinghrao@uclan.ac.uk.
Note: [1] These authors contributed equally to this work.
Abstract: Periodontitis is a polymicrobial chronic inflammatory disease of tooth-supporting tissues with bacterial etiology affecting all age groups, becoming chronic in a subgroup of older individuals. Periodontal pathogens Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are implicated in the development of a number of inflammatory pathologies at remote organ sites, including Alzheimer's disease (AD). The initial inflammatory hypothesis proposed that AD hallmark proteins were the main contributors of central nervous system (CNS) inflammation. This hypothesis is expanding to include the role of infections, lifestyle, and genetic and environmental factors in the pathogenesis of AD. Periodontal disease (PD) typifies a condition that encompasses all of the above factors including pathogenic bacteria. These bacteria not only are the source of low-grade, chronic infection and inflammation that follow daily episodes of bacteremia arising from everyday tasks such as brushing, flossing teeth, chewing food, and during dental procedures, but they also disseminate into the brain from closely related anatomical pathways. The long-term effect of inflammatory mediators, pathogens, and/or their virulence factors, reaching the brain systemically or otherwise would, over time, prime the brain's own microglia in individuals who have inherent susceptibility traits. Such susceptibilities contribute to inadequate neutralization of invading agents, upon reaching the brain. This has the capacity to create a vicious cycle of sustained local inflammatory milieu resulting in the loss of cytoarchitectural integrity and vital neurons with subsequent loss of function (deterioration in memory). The possible pathways between PD and AD development are considered here, as well as environmental factors that may modulate/exacerbate AD symptoms.
