Z-RNA drives Tau-mediated neurodegeneration of Alzheimer's disease [RIP-Seq]

Tau aggregates lead to progressive neurodegeneration in Alzheimer's disease (AD). 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. Overall design: ZBP1 or ZNA from 9-month-old PS19 and WT mice were pull down by corresponding antibodies.The immunoprecipitated RNA was purified for RNA sequencing.