Does the tau protein stop brain cells from sending inhibitory signals?

Research project: Progressive functional disruption of inhibitory neurons in tauopathy.

Lead Investigator: Dr Francesco Tamagnini
Institution: University of Reading
Grant type: Project 
Duration: 12 months
Amount: £63,007

Why did we fund this project?

Comments from members of our Research Network:

‘What he aims to do could be very important in tackling dementia. It could be well-worth supporting especially since he has a major drug company on-side.’

What do we already know?

We know that the brain is made up of complex circuits of brain cells which send and receive information from each other. Some of these information signals are ‘excitatory’ as they excite or turn up and action or response. Others are ‘inhibitory’ because they inhibit or turn down a response or action. Both excitatory and inhibitory signals create an essential balance which is essential for the brain to function properly.

The hippocampus is the area of the brain that makes new experiences into memories. The area of the hippocampus is also one of the first and most severely affected by the build-up of tau protein in Alzheimer’s disease. Tau protein builds up in twisted coils called tangles inside the brain cells of people who have Alzheimer’s disease. This build-up of tau is believed to prevent brain cells from working properly and ultimately die. 

It is important to understand how brain cells react to tau build-up. Dr Tamagnini and colleagues want to focus specifically on the brain cells that send out inhibitory signals to understand how the delicate balance of excitatory and inhibitory signals is disrupted in Alzheimer’s.

What does this project involve?

Dr Tamagnini will focus on the hippocampus which is severely affected by Alzheimer’s disease and several other forms of dementia. His team aim to understand how the build-up of tau protein affects the function of inhibitory signals in this area of the brain. The study will involve using delicate measuring techniques to learn about the electrical properties of inhibitory brain cells. In a way similar to testing whether the electrical wiring of a house stops working when the wires are damaged or blocked.  

The researchers will find out whether the electrical signalling of inhibitory brain cells can’t work when coils of tau get in the way. At the same time they will test whether the build-up of tau and the changes in electrical signalling affect the structure of the brain cell. 
Having learned from these, Dr Tamagnini will next move on to the most state-of the art technology of this project  -  use a specialised microscope to create beautiful images which tell him about how whole groups of brain cells are communicating with each other inside the brain.

How will it help people with dementia?

This research will be a huge help in explaining why tau causes brain cells in Alzheimer’s to stop working and die. This information will help us to understand more about what’s going on in Alzheimer’s but also other types of dementia such as Frontotemporal dementia.

Dr Tamagnini and his team believe that this research will help in the development of new treatments for Alzheimer’s disease. They have the support of the pharmaceutical company Eli Lilly who are working closely with them on this project and will work together to share results and ideas.