Inflammation as a potential mediator for the association between periodontal disease and Alzheimer's disease

Abstract

Periodontal disease (PDD) is associated with increased risk of cardiovascular disease, cerebrovascular disease, and mortality in many studies, while other studies have begun to suggest an association of PDD with Alzheimer's disease (AD). This paper discusses how infectious pathogens and systemic infection may play a role in AD. The roles of infection and inflammation are addressed specifically with regard to known AD pathologic lesions including senile plaques, neuron death, neurofibrillary tangles, and cerebrovascular changes. A testable model of proposed pathways between periodontal infection and AD is presented including three possible mechanisms: a) direct effects of infectious pathogens, b) inflammatory response to pathogens, and c) the effects on vascular integrity. The role of gene polymorphisms is discussed, including apolipoprotein (APOE) varepsilon4 as a pro-inflammatory and pro-infection genotype.

Keywords: Alzheimer’s disease; infection; inflammation; periodontal disease.

Figure 1

In periodontal disease, the gingiva recedes from the tooth forming pockets through which bacteria may more easily enter the bloodstream.

Figure 2

Proposed pathways between periodontal infection and Alzheimer’s disease pathology. Abbreviations: LPS, lipopolysaccharide; APP, amyloid precursor protein; AB, amyloid beta; NFTs, neurofibrillary tangles.