Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Bacterial Extracellular DNA Promotes β-amyloid Aggregation

Version 1 : Received: 22 May 2021 / Approved: 24 May 2021 / Online: 24 May 2021 (10:33:22 CEST)

A peer-reviewed article of this Preprint also exists.

Tetz, G.; Tetz, V. Bacterial Extracellular DNA Promotes β-Amyloid Aggregation. Microorganisms 2021, 9, 1301. Tetz, G.; Tetz, V. Bacterial Extracellular DNA Promotes β-Amyloid Aggregation. Microorganisms 2021, 9, 1301.

Journal reference: Microorganisms 2021, 9, 1301
DOI: 10.3390/microorganisms9061301

Abstract

Alzheimer’s disease is associated with prion-like aggregation of the amyloid β (Aβ) peptide and the subsequent accumulation of misfolded neurotoxic aggregates in the brain. Therefore, it is critical to clearly identify the factors that trigger the cascade of Aβ misfolding and aggregation. Numerous studies have pointed out the association between microorganisms and their virulence factors and Alzheimer’s disease; however, their exact mechanisms of action remain unclear. Recently, we discovered a new pathogenic role of bacterial extracellular DNA, triggering the formation of misfolded Tau aggregates. In this study, we investigated the possible role of DNA extracted from different bacterial and eukaryotic cells in triggering Aβ aggregation in vitro. Interestingly, we found that the extracellular DNA of some, but not all, bacteria is an effective trigger of Aβ aggregation. Furthermore, the acceleration of Aβ nucleation and elongation can vary based on the concentration of the bacterial DNA and the bacterial strain from which this DNA had originated. Our findings suggest that bacterial extracellular DNA might play a previously overlooked role in the Aβ protein misfolding associated with Alzheimer’s disease pathogenesis. Moreover, it highlights a new mechanism of how distantly localized bacteria can remotely contribute to protein misfolding and diseases associated with this process. These findings might lead to the use of bacterial DNA as a novel therapeutic target for the prevention and treatment of Alzheimer’s disease.

Subject Areas

Alzheimer’s disease; amyloid-beta; amyloid plaques; bacterial DNA; protein aggregation

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