Periodontal Pathogens and Associated Intrathecal Antibodies in Early Stages of Alzheimer’s Disease

Article type: Research Article

Authors: Laugisch, Oliver^{a; b; 1; *} | Johnen, Andreas^{c; 1} | Maldonado, Alejandra^d | Ehmke, Benjamin^a | Bürgin, Walter^e | Olsen, Ingar^f | Potempa, Jan^{g; h} | Sculean, Anton^d | Duning, Thomas^{c; 1} | Eick, Sigrun^{d; 1}

Affiliations: [a] Department of Periodontology, School of Dental Medicine, University of Muenster, Germany | [b] Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, The Netherlands | [c] Department of Neurology, University Hospital Muenster (UKM), University of Muenster, Germany | [d] Department of Periodontology, School of Dental Medicine, University of Bern, Switzerland | [e] Research section, School of Dental Medicine, University of Bern, Switzerland | [f] Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway | [g] Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland | [h] Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, KY, USA

Correspondence: [*] Correspondence to: Oliver Laugisch, Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Gustav Malerlaan 3004, 1081 LA Amsterdam, The Netherlands. Tel.: +31 20 5980888; E-mail: o.laugisch@acta.nl.

Note: [1] These authors contributed equally to this work.

Abstract: Background: Recent studies suggest a link between periodontitis and Alzheimer’s disease (AD). Objective:Verification of the presence of periodontal pathogens and the intrathecal generation of pathogen-specific antibodies in 20 patients with AD and 20 with other forms of dementia (DEM-noAD). Methods:Clinical periodontal indices were recorded. Cerebrospinal fluid (CSF) was analyzed for total tau protein (T-tau) and amyloid-β (Aβ1-42). In serum and CSF, antibody levels against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema species were quantified. The presence of selected bacteria and inflammatory biomarkers were determined in periodontium, serum, and CSF. Results: In line with diagnoses, CSF-levels of Aβ1-42 were significantly lower in AD than DEM-noAD patients. Periodontal destruction and inflammation were omnipresent with no difference between groups. P. gingivalis, T. forsythia, and Treponema species were detected in more than 50% of subgingival biofilm samples, but neither in serum nor in the CSF. Elevated levels of anti-pathogen antibodies in CSF of 16 patients (7 AD; 9 DEM-noAD) compared to serum highlight a possibility of the intrathecal immune response to pathogens. There was no significant difference in antibodies levels against selected bacteria in CSF and serum between groups. Multivariate regression analysis and general linear models revealed an association of the T-tau level in AD group with both serum levels of anti-P. gingivalis antibodies and MCP-1/CCL-2. Conclusion: Periodontal pathogens may enter the brain and stimulate a local immune response. However, in patients with dementia at the age up to 70 years, periodontal pathogens do not act as a trigger for developing AD.

Keywords: Alzheimer’s disease, dementia, periodontitis, periodontal pathogens, Porphyromonas gingivalis

DOI: 10.3233/JAD-180620

Journal: Journal of Alzheimer's Disease, vol. 66, no. 1, pp. 105-114, 2018