Are Porphyromonas gingivalis Outer Membrane Vesicles Microbullets for Sporadic Alzheimer’s Disease Manifestation?

Abstract

Our research into Alzheimer’s disease (AD) focuses on the oral cavity and the brain, from which key evaluations of prospective and retrospective population based data have shown that chronic periodontal disease existing for ten-years or over doubles the risk for the sporadic form of AD. Furthermore, Porphyromonas gingivalis mono-infections in established periodontal lesions, or introducing its lipopolysachharide (LPS), as demonstrated in vivo studies, show hallmark pathology inclusive of extracellular amyloid plaques and phospho-tau bound neurofibrillary tangles with AD-like phenotype. Other studies have shown that if periodontitis remains untreated in human AD patients, cognitive decline ensues. This is a bi-directional relationship meaning that the converse is also true; treating periodontal disease in AD patients improves memory. Bacterial cultures and established oral biofilms generate vast numbers of microvesicles and P. gingivalis outer membrane vesicles encase key virulence factors (LPS, gingipains, capsule, fimbriae) as though they are complete destructive “microbullets” when shed in the host. This provides P. gingivalis additional arsenal to manipulate its entry into disparate organs, hijack phagocytosis, destroy tissues, and affect complement related genes whilst transducing the onset of proinflammatory signalling cascades. The resulting inflammatory mediators may be the cause of disease defining lesions and cognitive decline typical of clinical AD.