The Role of Planar Cell Polarity Proteins in
Tau Oligomer-Induced Synapse Degeneration

Cognitive functions of the brain rely on communication among networks of neurons through their connections, called synapses. In Alzheimer’s disease, large numbers of synapses are lost early on and continue to be lost throughout disease progression, directly causing deterioration of memory and other brain functions. Currently, there is no effective therapy to protect these important synapses or to regenerate the lost synaptic connections.

Drs. Zou and Jiang’s team discovered the critical proteins that function in a signaling pathway to control the maintenance of synapses and found that some of them stabilize synapses, whereas others remove synapses. In the healthy brain, both stabilization and removal of synapses are important for learning and memory and are properly regulated. They found that the balance is altered in Alzheimer’s disease, such that the function of proteins stabilizing synapses is weakened by oligomeric Aβ, leading to excessive and uncontrolled loss of synapses. When the balance is restored by inhibiting the function of the molecules that remove synapses, they can protect synapses and memory as well as reverse symptoms of cognitive impairment in mouse models for Alzheimer’s. In this proposal, they will investigate whether and how toxic tau protein aggregates interact with these proteins and whether restoring the balance can protect synapses and memory. Their findings may lead to novel therapeutics to treat synapse and memory loss in Alzheimer’s disease.