Periodontitis and Alzheimer´s disease

Abstract

Background: Alzheimer's disease (AD), the main cause of dementia in the adult population, is characterized by a progressive loss of cognitive function. It is considered that neuroinflammation plays a fundamental role in its onset and progression. The bacteria present in the disbiotic microbiome generated during the course of periodontitis (PE) are capable of inducing a systemic inflammatory response, exacerbating the production of proinflammatory mediators that have the potential to spread to the systemic circulation.

Material and methods: A literature review was made using the databases Scielo, PubMed, EBSCO and key words "Alzheimer disease", "Periodontitis", "Neurodegeneration", "Inflammation mediators", "Elderly".

Results: Several hypotheses point to similar pathophysiological pathways in the establishment of AD and PE, sharing cellular and molecular proinflammatory characteristics. In periodontitis, locally produced cytokines and pro-inflammatory products spread from the ulcerated periodontal pocket into the systemic circulation, or around the trigeminal nerve terminals, which allows the passage of bacteria or their products to the brain. This fact leads to the formation of plaques of amyloid peptide and intraneuronal neurofibrillar tangles (NFTs) that activate the glial cells producing a significant increase in proinflammatory cytokines in the affected regions that lead to a loss of neuronal synapses and neurodegeneration, contributing to the progression of AD.

Conclusions: This review of the literature contributes to the understanding of the pathological pathways shared by both diseases such as oxidative damage and inflammation. There is not enough evidence to determine an association between this two pathologies, so it is considered necessary to conduct studies for determine if periodontitis is capable of inducing or exacerbating the neuroinflammation that will trigger AD.

Figure 1

Common pathophysiological pathways between AD and periodontitis. The increase in inflammatory activity is the point of confluence between AD and periodontitis. As a result of the activity of periodontopathogens on the one hand and microglial activation on the other, an increase in the levels of the main proinflammatory molecules and their metabolites is produced, when this state is maintained in the long term it generates tissue destruction.

Figure 2

Neuroinflammatory hypotesis in the establishment of AD. When the inflammatory state is persistent, microglia and astrocytes modify their phenotype to reactive cells, increasing the secretion of pro-inflammatory cytokines and generating a metabolic, energetic and oxidative imbalance in the neuron that will respond by increasing the production of Aβ and the hyperphosphorylation of the microtubule-associated protein, Tau, events that generate neuro and synaptotoxicity.

Figure 3

Inflammatory response of brain cells to oral bacteria. Model that suggests that periodontal bacteria and their products can invade the brain via and possibly generate a local inflammatory response and neurotoxicity.