Affiliations: [a] Oral & Dental Sciences Research Group, School of Postgraduate Medical and Dental Education, University of Central Lancashire, Preston, UK | [b] Department of Periodontology and Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA | [c] Blizard Institute of cell & Molecular Science, Barts & The London School of Medicine and Dentistry, London, UK
Correspondence:
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Correspondence to: Dr. S.K. Singhrao, Oral & Dental Sciences Research Group, School of Postgraduate Medical and Dental Education, University of Central Lancashire, Preston, PR1 2HE, UK. Tel.: +44 1772 895137; Fax: +44 1772 892965; E-mail: [email protected].
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.
