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

被引:58
作者
Laugisch, Oliver [1 ,2 ,3 ]
Johnen, Andreas [4 ]
Maldonado, Alejandra [5 ]
Ehmke, Benjamin [1 ]
Buergin, Walter [6 ]
Olsen, Ingar [7 ]
Potempa, Jan [8 ,9 ]
Sculean, Anton [5 ]
Duning, Thomas [4 ]
Eick, Sigrun [5 ]
机构
[1] Univ Munster, Sch Dent Med, Dept Periodontol, Munster, Germany
[2] Univ Amsterdam, Acad Ctr Dent Amsterdam ACTA, Dept Oral Cell Biol, Gustav Malerlaan 3004, NL-1081 LA Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Gustav Malerlaan 3004, NL-1081 LA Amsterdam, Netherlands
[4] Univ Munster, Univ Hosp Muenster UKM, Dept Neurol, Munster, Germany
[5] Univ Bern, Sch Dent Med, Dept Periodontol, Bern, Switzerland
[6] Univ Bern, Sch Dent Med, Res Sect, Bern, Switzerland
[7] Univ Oslo, Fac Dent, Dept Oral Biol, Oslo, Norway
[8] Jagiellonian Univ, Fac Biochem Biophys & Biotechnology, Dept Microbiol, Krakow, Poland
[9] Univ Louisville, Sch Dent, Dept Oral Immunol & Infect Dis, Louisville, KY 40292 USA
关键词
Alzheimer's disease; dementia; periodontitis; periodontal pathogens; Porphyromonas gingivalis; GINGIVAL CREVICULAR FLUID; MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; PORPHYROMONAS-GINGIVALIS; CEREBROSPINAL-FLUID; VIRULENCE FACTORS; AMYLOID-BETA; DEMENTIA; DIAGNOSIS; INFLAMMATION;
D O I
10.3233/JAD-180620
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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-beta (A beta(1-)(42)). In serum and CSF, antibody levels against Porphyromonas gingivalis, Aggregatibacter actinomycetem-comitans, 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 A beta(1-)(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.
引用
收藏
页码:105 / 114
页数:10
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