Bi-directional relationship between the biofilm of Porphyromonas gingivalis and the amyloid-beta peptide.

Dumoulin, D.; Ghrayeb, M.; Cote, S.; Garneau, D.; Chai, L.; Frost, E.; Fülöp, T.; Beauregard, P. B.

doi:10.1101/2025.05.16.654480

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bioRxiv · 10.1101/2025.05.16.654480

Bi-directional relationship between the biofilm of Porphyromonas gingivalis and the amyloid-beta peptide.

Dumoulin, D.·Ghrayeb, M.·Cote, S.·Garneau, D.·Chai, L.·Frost, E.·Fülöp, T.·Beauregard, P. B.

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Abstract

Periodontitis and Porphyromonas gingivalis infections are significant risk factors for the onset of Alzheimers disease (AD). Despite P. gingivalis relying on biofilm for its survival and virulence, the impact of the extracellular matrix on ADs neuropathological hallmarks was never examined. In this study, we report a bidirectional relationship between the amyloid beta (A{beta}) peptide, which plays a central role in AD, and the biofilm of P. gingivalis. Using multiple fluorescent markers for biofilm components, we observed that A{beta}1-40 inhibited biofilm formation while A{beta}1-42 increased extracellular matrix production. Also, using thioflavin T staining and atomic force microscopy, we observed co-aggregation between the biofilm and monomeric A{beta}1-40, resulting in a quicker aggregation and significant changes in aggregate structures. Our findings propose mechanistic explanations for the role of P. gingivalis as a risk factor for AD and offer potential mechanisms for the microbial involvement in AD etiology. ImportanceWhile the etiology of Alzheimers disease has been studied extensively for the past 50 years, its exact causes remain unknown. Our current understanding is that the accumulation of multiple genetic and environmental risk factors would lead to the onset of the disease. Porphyromonas gingivalis is a bacterium that produces biofilm and elicits periodontitis, a chronic infection of the gums that constitutes a risk factor for Alzheimers disease. While studies have looked at the effects of P. gingivalis in triggering Alzheimers symptoms in animal models, none have explored the impact of the biofilm, which is ubiquitous to this bacterium. Our study seeks to bridge that gap by demonstrating a bi-directional relationship between the biofilm of P. gingivalis and amyloid beta, one of the brain lesions involved in Alzheimers. By understanding risk factors involved in Alzheimers and their impact, we hope to provide valuable knowledge on prevention and treatment.

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Dumoulin, D., Ghrayeb, M., Cote, S., Garneau, D., Chai, L., Frost, E., Fülöp, T., Beauregard, P. B.. 2025-05-17. Bi-directional relationship between the biofilm of Porphyromonas gingivalis and the amyloid-beta peptide.. https://doi.org/10.1101/2025.05.16.654480

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