Extended Data Fig. 9: TERT contributes to β-Catenin/TCF-mediated transactivation in AD neurons.

At the early pathological stage of AD, Aβ oligomers induce the transcriptional repression of TERT gene via the propagation of heterochromatin in neurons. Genetic depletion and pharmacological inhibition of H3K9 methyltransferases (HMTs) can de-repress TERT gene suppression. TERT protein is able to interact with RNA pol II core transactivation machinery through β-Catenin and triggers the transcriptional induction of specific genes associated with neuronal survival and synaptic function in AD neurons, enabling to alleviate cognitive deficits.