Can better management of periodontal disease delay the onset and progression of Alzheimer’s disease?

Harding, Alice, Robinson, Sarita Jane orcid iconORCID: 0000-0002-4237-5412, Crean, Stjohn orcid iconORCID: 0000-0001-9336-8549 and Singhrao, Simarjit Kaur orcid iconORCID: 0000-0001-9573-5963 (2017) Can better management of periodontal disease delay the onset and progression of Alzheimer’s disease? Journal of Alzheimer’s Disease, 58 (2). pp. 337-348. ISSN 1387-2877

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Official URL: http://doi.org/10.3233/JAD-170046

Abstract

A risk factor relationship exists between periodontal disease and Alzheimer’s disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P. gingivalis, to gain greater virulence. The initial process involves P. gingivalis disturbing neutrophil mediated innate immune responses in the healthy gingivae and then downregulating adaptive immune cell differentiation and development to invade, and subsequently, establish new dysbiotic bacterial communities. Immune responses affect the host in general and functionally via dietary adjustments caused by tooth loss. Studies from animals orally infected with P. gingivalis confirm this bacterium can transmigrate to distant organ sites (the brain) and contribute towards peripheral and intracerebral inflammation, and compromise vascular and microvascular integrity. In another study, P. gingivalis infection caused sleep pattern disturbances by altering glial cell light/dark molecular clock activity, and this, in turn, can affect the clearance of danger associated molecular patterns, such as amyloid-beta, via the glymphatic system. Since, P. gingivalis can transmigrate to the brain, and modulate organ-specific inflammatory innate and adaptive immune responses, this paper explores whether better management of indigenous periodontal bacteria could delay/prevent the onset and/or progression of dementia.


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