How does tau, a hallmark of Alzheimer's disease, affect the connections between brain cells?

Read about a research project we funded into the mechanisms of tau-induced synapse loss in Alzheimer’s disease.

Lead Investigator: Dr Tara Spires-Jones

  • Institution: University of Edinburgh
  • Grant type: PhD studentship
  • Amount: £84,700
  • Start date: September 2014
  • End date: September 2017

What was the aim for the project?

Synapses, the connections between nerve cells are vital for forming memories. In Alzheimer’s these connections can dysfunction and cause the cells to die. The protein, tau is known to form tangles in the areas of the brain important for memory and then move through the brain as symptoms progress. 

In this project, the researchers aimed to find out if tau caused these synapses to malfunction and find out why this might happen. They also looked at whether the movement of mitochondria (the energy producing batteries of our cells) was impaired and caused damage to synapses as they were not present to provide enough energy.

What did the researchers do?

Dr Spires-Jones and her team used models of Alzheimer’s and donated human brain tissue. The team added markers to the brain tissue to identify synapses and mitochondria. These images helped the research team find out whether synapses were lost when tau was present and how tau affects the movement of mitochondria to synapses.

What were the key results?

The team found that the building blocks of amyloid-beta (another protein associated with Alzheimer’s) were present at some of synapses of the nerve cells. The team believe these blocks contributed to the loss of the connections. 

The abnormal tau protein was also present at the synapses but the research team showed that tau spreads between the nerve cells before the connections break down. This suggests that the spread of tau begins at the very early stages of the condition. 

Dr Spires-Jones also found in the human brain tissue, fewer mitochondria were found at the synapses when tau and amyloid-beta were present.

What were the key results?

The team found that the building blocks of amyloid-beta (another protein associated with Alzheimer’s) were present at some of synapses of the nerve cells. The team believe these blocks contributed to the loss of the connections. 

The abnormal tau protein was also present at the synapses but the research team showed that tau spreads between the nerve cells before the connections break down. This suggests that the spread of tau begins at the very early stages of the condition.

Dr Spires-Jones also found in the human brain tissue, fewer mitochondria were found at the synapses when tau and amyloid-beta were present.

How will this help in the fight against dementia?

Finding out why synapses die during Alzheimer’s disease is an essential step towards developing treatments for the disease. This project has added to the growing body of evidence that the level of abnormal tau is an important target for stopping or slowing down Alzheimer’s.

However it also highlights how complex the breakdown of the connections between nerve cells is. The team have shown that ideally a therapy will need to target both tau and amyloid-beta.

If we can understand the changes that happen at these vital synapses and the role of mitochondria we will be able to target a treatment that prevents their breakdown.   

What are the next steps?

Eleanor Pickett, who has submitted her PhD, has started a postdoctoral position. In her research she will now be aiming to understand further:

  • The role of mitochondria at the synapses in donated brain tissue.
  • The interaction of tau and amyloid-beta at the synapses in a new mouse model

Sharing this research

Eleanor published her findings in a number of scientific publications including:

  • Pickett EK et al. (2017) Spread of tau down neural circuits precedes synapse and neuronal loss in the rTgTauEC mouse model of early Alzheimer’s disease. Synapse 71:e21965. https://doi.org/ 10.1002/syn.21965
Think this page could be useful to someone? Share it:
Categories

Further reading