Proteins translated from tau circular RNAs as drivers for Alzheimer's disease and frontotemporal dementia.

Our data indicate that MAPT circular RNAs are translated into proteins that could cause tau aggregations relevant to tauopathies. As most FTLD-tau causing mutations are in the regions near the circularizing part of the gene, they could act through regulating circular RNA formation and/or translation. ADAR-dependent upregulation of circTau translations caused by inflammation and/or brain injury could trigger tau pathology via this mechanism. Finally, tau circRNA can be selectively removed using siRNAs. We are assessing the impact of MAPT circRNAs on proteinaceous aggregations.