Periodontal microorganisms and Alzheimer disease - A causative relationship?

Abstract

In the initiation or exacerbation of Alzheimer disease, the dissemination of oral microorganisms into the brain tissue or the low-level systemic inflammation have been speculated to play a role. However, the impact of oral microorganisms, such as Porphyromonas gingivalis, on the pathogenesis of Alzheimer disease and the potential causative relationship is still unclear. The present review has critically reviewed the literature by examining the following aspects: (a) the oral microbiome and the immune response in the elderly population, (b) human studies on the association between periodontal and gut microorganisms and Alzheimer disease, (c) animal and in vitro studies on microorganisms and Alzheimer disease, and (d) preventive and therapeutic approaches. Factors contributing to microbial dysbiosis seem to be aging, local inflammation, systemic diseases, wearing of dentures, living in nursing homes and no access to adequate oral hygiene measures. Porphyromonas gingivalis was detectable in post-mortem brain samples. Microbiome analyses of saliva samples or oral biofilms showed a decreased microbial diversity and a different composition in Alzheimer disease compared to cognitively healthy subjects. Many in-vitro and animal studies underline the potential of P gingivalis to induce Alzheimer disease-related alterations. In animal models, recurring applications of P gingivalis or its components increased pro-inflammatory mediators and β-amyloid in the brain and deteriorated the animals' cognitive performance. Since periodontitis is the result of a disturbed microbial homoeostasis, an effect of periodontal therapy on the oral microbiome and host response related to cognitive parameters may be suggested and should be elucidated in further clinical trials.

FIGURE 1

Microglial main functions, that is, immune vigilance, synaptic pruning, and phagocytosis and their level of activity undergo a circle throughout life. The checkpoint mechanisms help to regulate these alterations. Adapted by permission from: Springer Nature, Nature Neuroscience, Deczkowska et al. 2018.