Z-RNA drives Tau-mediated neurodegeneration of Alzheimer’s disease

Neuron death is one of the hallmarks of neurodegeneration. However, the pathological influence of neuronal death is undetermined, and the connection between Tau aggregates and neuronal death remains elusive.

Here we demonstrated the essential role of neuron death in Tau-related neurodegeneration. Tau-neurons died in necroptosis, dependent on ZBP1 sensitized by Z-RNAs (an unusual left-handed conformation). Those endogenous Z-RNAs were transcripts of reactivated transposable elements (TEs) originally silenced in heterochromatin.