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Sci Rep. 2020 Feb 11;10(1):2369. doi: 10.1038/s41598-020-59364-x.

Bacterial DNA promotes Tau aggregation.

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Human Microbiology Institute, New York, NY, 10013, USA.
Tetz Laboratories, New York, NY, 10013, USA.
Mitchell Center for Alzheimer's disease and related brain disorders, Department of Neurology, University of Texas McGovern Medical School, Houston, TX, 77030, USA.
Human Microbiology Institute, New York, NY, 10013, USA.


A hallmark feature of Alzheimer's disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.

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