Data from paper: Evidence for trans-synaptic propagation of oligomeric tau in human Progressive Supranuclear Palsy

In the neurodegenerative disease Progressive Supranuclear Palsy (PSP), tau pathology progresses through the brain in a stereotypical spatiotemporal pattern, and where tau pathology appears, synapses are lost. We tested the hypothesis that pathological tau contributes to synapse loss and may spread through the brain by moving from pre- to post-synapses. Using post-mortem PSP brain samples and a living human brain slice culture model, we observe pathological tau in synaptic pairs and evidence that oligomeric tau can enter live human post-synapses. Proteomics revealed increased clusterin in synapses in PSP, and super-resolution imaging showed clusterin colocalised with tau in synapses in close enough proximity to be binding partners, which may mediate tau spread. Accumulation of tau in synapses correlated with synapse loss, and synaptic engulfment by astrocytes was observed, suggesting that astrocytes contribute to synapse loss. Together these data indicate that targeting synaptic tau is a promising approach to treat PSP.