Tau condensates control clustering of recycling synaptic vesicles

For the first time, the researchers have shown how the tau protein, known for its role in dementias, behaves where communication in the brain takes place.

The study used super-resolution microscopy to visualise individual tau proteins in motion while neurons are “talking” to each other.

“We discovered that tau in a healthy brain controls an important population of vesicles at the presynapse critical for neuronal communication,” the author said.

“These vesicles are like the words that neurons use to transmit information to other neurons.

"For the very first time, we’ve shed light on the mechanism by which tau acts in our nerve cells.

“By understanding tau’s role in a healthy context, we begin to fully understand what leads to the abnormal accumulation of tau in disease.”

The author said that observing tau’s behaviour in healthy states provides clues to how these toxic aggregates start to form.

“Studying tau in a healthy brain is more challenging than studying it in a diseased brain, where changes in its molecular behaviour are far more prominent and obvious,” the author said.

“But by visualising tau at the nanoscale and in this context, we can identify the molecular behaviours that precede the formation of toxic protein aggregates in disease.”

The team also discovered that tau molecules form tiny condensates, dense gel-like bodies within brain cells, which resemble oil droplets suspended in water.

“What we noticed is that these tau condensates are very fluid-like and dynamic and are tightly regulated by synaptic activity,” the author said.

“In neurodegenerative disorders, these condensates get bigger and denser and eventually form aggregates, which are destructive to brain function.

“Our next challenge is to track diseased tau in brain cells to see how this new function is altered, leading to tau aggregation.”