Do Periodontal Pathogens or Associated Virulence Factors Have a Deleterious Effect on the Blood-Brain Barrier, Contributing to Alzheimer's Disease?

Abstract

The central nervous system (CNS) is protected by a highly selective barrier, the blood-brain barrier (BBB), that regulates the exchange and homeostasis of bloodborne molecules, excluding xenobiotics. This barrier forms the first line of defense by prohibiting pathogens from crossing to the CNS. Aging and chronic exposure of the BBB to pathogens renders it permeable, and this may give rise to pathology in the CNS such as Alzheimer's disease (AD). Researchers have linked pathogens associated with periodontitis to neuroinflammation and AD-like pathology in vivo and in vitro. Although the presence of periodontitis-associated bacteria has been linked to AD in several clinical studies as DNA and virulence factors were confirmed in brain samples of human AD subjects, the mechanism by which the bacteria traverse to the brain and potentially influences neuropathology is unknown. In this review, we present current knowledge about the association between periodontitis and AD, the mechanism whereby periodontal pathogens might provoke neuroinflammation and how periodontal pathogens could affect the BBB. We suggest future studies, with emphasis on the use of human in vitro models of cells associated with the BBB to unravel the pathway of entry for these bacteria to the CNS and to reveal the molecular and cellular pathways involved in initiating the AD-like pathology. In conclusion, evidence demonstrates that bacteria associated with periodontitis and their virulence factors are capable of inflecting damage to the BBB and have a role in giving rise to pathology similar to that found in AD.

Keywords: Alzheimer’s disease; bacteria; blood-brain barrier; periodontitis; virulence factors.