Investigating the role of tau in mechanisms of synaptic resilience

The loss of connections between brain cells, called synapses, contributes to memory and thinking difficulties in Alzheimer’s disease. Recent studies show that the brain can compensate for this, creating new synapses or making existing ones bigger. Tau protein is known for forming harmful clumps and damaging synapses in Alzheimer’s.

However, in normal conditions tau is important for keeping synapses healthy. This study aims to understand how tau affects the brain’s ability to compensate for the loss of synapses.

Specifically, we will focus on tiny structures on the branches of neurons called dendritic spines, which are part of most synapses.

To achieve this, we will recreate the loss of synapses seen in Alzheimer’s in mouse brain slices, which will have normal tau, harmful tau, or no tau at all.

We will analyse how dendritic spines react to the loss of synapses in these different conditions, monitoring their number, size, and function over time.

Finally, we will do a similar study using slices of human brain samples, obtained from patients who have had brain surgery.

By doing this, we hope to reveal new roles of tau in synapses, which could help develop better treatments for Alzheimer’s.