Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer's disease brain tissue.

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.