Investigation of the Bacterial Associations between Periodontitis and Alzheimer’s Disease

Abstract

Background: There is growing, yet inconclusive evidence of a causal association between periodontitis and Alzheimer’s disease (AD). The role of bacteria in this potentially contributory relationship is not fully understood and the effectiveness of conventional periodontal treatment for those with AD remains uncertain.

Aim: To investigate the salivary, blood and brain bacterial composition associated with periodontitis and AD, and the feasibility of treating periodontitis in AD patients.

Methods: Bacterial profiles of saliva, blood and brain tissue from human cohorts were analysed using 16SrDNA polymerase chain reactions and next generation sequencing to characterise bacterial composition in health and disease. A pilot clinical study was conducted to investigate the feasibility of treating periodontitis in those who have mild AD.

Results: Salivary and blood bacterial constituents were significantly different in periodontitis compared to controls; oral bacteria were a major source of blood bacteria. The feasibility of treating AD participants with periodontitis (ADP) was proven; significant reductions in clinical markers of periodontitis indicate that this treatment was successful at 12-24 months. Bacterial profiles in ADP saliva were significantly different from non-AD periodontitis and controls. Oral bacteria were identified in brain tissue from those with AD and controls. There were distinct differences in the bacterial profiles of Entorhinal cortex and Locus Coeruleus, known to be implicated in early AD development, compared to other areas.

Conclusion: Oral bacteria, including periodontal pathogens, were capable of reaching the systemic circulation in viable form and were identified as part of a diverse range of bacteria detected across multiple brain areas. It is therefore biologically plausible that periodontal and oral bacteria could influence the trajectory of AD. Treatment of periodontitis was demonstrated to be effective in the early stage of AD. Future AD periodontal treatment randomized controlled trials will identify whether this can modify cognitive decline in AD.

Date of Award	18 Mar 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Nicola X West (Supervisor), Shelley J Allen Allen-Birt (Supervisor) & Maria Davies (Supervisor)