Cellular Reprogramming Rescues Memory-Encoding Neurons
EPFL researchers used a doxycycline-gated dual-AAV system to express OSK (Oct4, Sox2, Klf4) selectively in learning-activated engram neurons. Targeted partial reprogramming rescued memory performance and remote recall in aged mice and APP/PS1 and 5xFAD Alzheimer models, reversed cellular aging hallmarks while preserving neuronal identity, and reduced predicted cognitive age. Effects were replicated across hippocampus and medial prefrontal cortex, with preferential reactivation of reprogrammed engram cells during recall.
Why it mattersEPFL's OSK engram reprogramming restores memory in APP/PS1 Alzheimer models, suggesting clinical trial prioritization.