Periodontitis, Microbiomes and their Role in Alzheimer's Disease

Abstract

As far back as the eighteenth and early nineteenth centuries, microbial infections were responsible for vast numbers of deaths. The trend reversed with the introduction of antibiotics coinciding with longer life. Increased life expectancy however, accompanied the emergence of age related chronic inflammatory states including the sporadic form of Alzheimer's disease (AD). Taken together, the true challenge of retaining health into later years of life now appears to lie in delaying and/or preventing the progression of chronic inflammatory diseases, through identifying and influencing modifiable risk factors. Diverse pathogens, including periodontal bacteria have been associated with AD brains. Amyloid-beta (Aβ) hallmark protein of AD may be a consequence of infection, called upon due to its antimicrobial properties. Up to this moment in time, a lack of understanding and knowledge of a microbiome associated with AD brain has ensured that the role pathogens may play in this neurodegenerative disease remains unresolved. The oral microbiome embraces a range of diverse bacterial phylotypes, which especially in vulnerable individuals, will excite and perpetuate a range of inflammatory conditions, to a wide range of extra-oral body tissues and organs specific to their developing pathophysiology, including the brain. This offers the tantalizing opportunity that by controlling the oral-specific microbiome; clinicians may treat or prevent a range of chronic inflammatory diseases orally. Evolution has equipped the human host to combat infection/disease by providing an immune system, but Porphyromonas gingivalis and selective spirochetes, have developed immune avoidance strategies threatening the host-microbe homeostasis. It is clear from longitudinal monitoring of patients that chronic periodontitis contributes to declining cognition. The aim here is to discuss the contribution from opportunistic pathogens of the periodontal microbiome, and highlight the challenges, the host faces, when dealing with unresolvable oral infections that may lead to clinical manifestations that are characteristic for AD.

Keywords: Alzheimer’s disease; functional amyloids; infections; microbiomes; periodontitis.

Figure 1

Schematic illustrating the macroscopic features relating to shrinkage (wider sulci, compared with non-Alzheimer’s disease (AD) brain), unique to the AD brain, which equates to inflammatory condition. The pathogens disrupt the epithelial cell-to-cell proteins of the gingivae through their proteases. The epithelial/endothelial barriers of capillaries disrupted for effective bacteremia to take place. The olfactory nerve pathways exploited to evade immune recognition. Environmental factors are the inflammophilic microbes with potential to subvert hosts immune defenses that also contribute to common inflammatory activities/pathways (p’ways) as well as contributing to proteostasis. At this stage the brain’s resilience is markedly compromised and the blood-brain barrier (BBB) is becoming defective. The endotoxin intolerance/further inflammation tip the brain into disease.