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Nature Neuroscience (1)

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Tau aggregates cause reactivation of transposable DNA elements, leading to Z-RNA–ZBP1-mediated neuronal death

Tau aggregates disrupt heterochromatin by sequestering H3K9me3, reactivating transposable elements. This generates Z-RNAs, activating ZBP1 to drive neuronal death. ZBP1 haploinsufficiency reverses cognitive decline in aged tau mice, offering a therapeutic target for tauopathies.

Wei Liu
Song-Ang Wu
Wei Mo
Research20 May 2026
Nature Neuroscience

P: 1-14

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Tau aggregates cause reactivation of transposable DNA elements, leading to Z-RNA–ZBP1-mediated neuronal death

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