Basic Science and Pathogenesis.

Background: Synapses can modify their strength in response to activity, and the unique properties of synapses that regulate their plasticity are essential for memory. Long-term potentiation (LTP) is considered the physiological basis for how neurons encode new memories. A complex series of postsynaptic signaling events in LTP is associated with memory deficits in tauopathy models, but the mechanism by which pathogenic tau inhibits plasticity at synapses is unknown.

KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss.

Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we define a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIdney/BRAin (KIBRA) protein (CT-KIBRA). We show that CT-KIBRA restores plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss.