Determining the Presence of Periodontopathic Virulence Factors in Short-Term Postmortem Alzheimer's Disease Brain Tissue

Abstract

The aim of this study was to establish a link between periodontal disease and Alzheimer's disease (AD) with a view to identifying the major periodontal disease bacteria (Treponema denticola, Tannerella forsythia, and Porphyromonas gingivalis) and/or bacterial components in brain tissue from 12 h postmortem delay. Our request matched 10 AD cases for tissue from Brains for Dementia Research alongside 10 non-AD age-related controls with similar or greater postmortem interval. We exposed SVGp12, an astrocyte cell line, to culture supernatant containing lipopolysaccharide (LPS) from the putative periodontal bacteria P. gingivalis. The challenged SVGp12 cells and cryosections from AD and control brains were immunolabeled and immunoblotted using a battery of antibodies including the anti-P. gingivalis-specific monoclonal antibody. Immunofluorescence labeling demonstrated the SVGp12 cell line was able to adsorb LPS from culture supernatant on its surface membrane; similar labeling was observed in four out of 10 AD cases. Immunoblotting demonstrated bands corresponding to LPS from P. gingivalis in the SVGp12 cell lysate and in the same four AD brain specimens which were positive when screened by immunofluorescence. All controls remained negative throughout while the same four cases were consistently positive for P. gingivalis LPS (p = 0.029). This study confirms that LPS from periodontal bacteria can access the AD brain during life as labeling in the corresponding controls, with equivalent/longer postmortem interval, was absent. Demonstration of a known chronic oral-pathogen-related virulence factor reaching the human brains suggests an inflammatory role in the existing AD pathology.

Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

“…During neurodegenerative processes, it has been hypothesized that a higher concentration of Ca ++ activates citrullination [15] but, P. gingivalis LPS and intact citrulline constitute potential contributory factors [68]. …”

Periodontal Disease as a Possible Risk Factor for Alzheimer’s Disease

“…Porphyromonas gingivalis, a periodontal disease-related bacteria, was found at high frequency in the autopsied brain tissue of patients who died of AD; however, it is not found in normal human brain tissue [26]. This result suggests that said bacteria spread hematogenously into the brain.…”

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling

“…This is noteworthy since peripheral blood mononuclear cells from periodontitis patients show increased levels of autophagy-related gene expression and high levels of mitochondrial reactive oxygen species, with further increase in LC3 upon stimulation of gingival fibroblasts with P. gingivalis LPS [55]. The ability to dysregulate autophagy in phagocytic cells has implications for development of distant organ inflammatory diseases in which either P. gingivalis or its LPS have been detected or been tested experimentally [56,57]. …”