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, 8 (3), 196-203

Serum Antibodies to Periodontal Pathogens Are a Risk Factor for Alzheimer's Disease

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Serum Antibodies to Periodontal Pathogens Are a Risk Factor for Alzheimer's Disease

Pamela Sparks Stein et al. Alzheimers Dement.

Abstract

Background: Chronic inflammation in periodontal disease has been suggested as a potential risk factor in Alzheimer's disease (AD). The purpose of this study was to examine serum antibody levels to bacteria of periodontal disease in participants who eventually converted to AD compared with the antibody levels in control subjects.

Methods: Serum samples from 158 participants in the Biologically Resilient Adults in Neurological Studies research program at the University of Kentucky were analyzed for immunoglobulin G antibody levels to seven oral bacteria associated with periodontitis, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Treponema denticola, Fusobacterium nucleatum, Tannerella forsythia, and Prevotella intermedia. All 158 participants were cognitively intact at baseline venous blood draw. In all, 81 of the participants developed either mild cognitive impairment (MCI) or AD or both, and 77 controls remained cognitively intact in the years of follow-up. Antibody levels were compared between controls and subjects with AD at baseline draw and after conversion and controls and subjects with MCI at baseline draw and after conversion using the Wilcoxon rank-sum test. AD and MCI participants were not directly compared. Linear regression models were used to adjust for potential confounding.

Results: Antibody levels to F nucleatum and P intermedia were significantly increased (α = 0.05) at baseline serum draw in the patients with AD compared with controls. These results remained significant when controlling for baseline age, Mini-Mental State Examination score, and apolipoprotein epsilon 4 status.

Conclusions: This study provides initial data that demonstrate elevated antibodies to periodontal disease bacteria in subjects years before cognitive impairment and suggests that periodontal disease could potentially contribute to the risk of AD onset/progression. Additional cohort studies profiling oral clinical presentation with systemic response and AD and prospective studies to evaluate any cause-and-effect association are warranted.

Figures

Figure 1
Figure 1
Figure 1A and 1B. Levels of IgG antibodies to the common periodontal pathogens Ag-gregatibacter actinomycetemcomitans (Aa), Campylobacter rectus (Cr), Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf), are compared in five groups of subjects: controls from the BRAINS group who remained cognitively intact (n=77 dark blue bar); subjects who eventually converted to AD at baseline serum draw (n= 35, red bar, AD before); subjects who converted to AD after conversion, at AD diagnosis (n=35 green bar, AD after); subjects who eventually converted to MCI at baseline serum draw (n=46, purple bar, MCI before); subjects who converted to MCI after conversion, at MCI diagnosis (n=46, light blue bar, MCI after). The mean raw data values are presented in the figures, although the p-values for the adjusted means were based on models where the outcome was the log-transformed values.
Figure 1
Figure 1
Figure 1A and 1B. Levels of IgG antibodies to the common periodontal pathogens Ag-gregatibacter actinomycetemcomitans (Aa), Campylobacter rectus (Cr), Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf), are compared in five groups of subjects: controls from the BRAINS group who remained cognitively intact (n=77 dark blue bar); subjects who eventually converted to AD at baseline serum draw (n= 35, red bar, AD before); subjects who converted to AD after conversion, at AD diagnosis (n=35 green bar, AD after); subjects who eventually converted to MCI at baseline serum draw (n=46, purple bar, MCI before); subjects who converted to MCI after conversion, at MCI diagnosis (n=46, light blue bar, MCI after). The mean raw data values are presented in the figures, although the p-values for the adjusted means were based on models where the outcome was the log-transformed values.

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