Understanding how brain cells called astrocytes prevent toxic tau from causing nerve cell death

Research project: Impact and characteristics of astrocytes in tau-related neurodegeneration

Lead Investigator: Professor Maria Grazia Spillantini
Institution: University of Cambridge  
Grant type: Project Grant 
Duration: 36 months
Amount: £248,520

Why did we fund this project?

Comments from members of our Research Network:

'This is an important target for disease progression and a good background leading to significant next step research.'

'This seems an important study which should be supported.'

'I can see that protecting and prolonging the life of neurons is key to fighting Alzheimer's disease.'

What do we already know?

Alzheimer's disease is characterised by the presence of two abnormal proteins in the brain. These proteins are called amyloid and tau. Researchers aren't exactly sure what the role of these proteins are or what their relationship is to each other. Most treatments that have been tested so far have targeted the amyloid protein but these have frequently failed. Therefore many researchers are focusing on understanding more about the role of the tau protein.

A lot of research has focused on the role of tau in nerve cells in the brain. However, tau also affects other brain cells, including astrocytes. Astrocytes are supporting cells, which help to keep neurons alive by providing them with nutrients and clearing away toxic debris. 

What does this project involve?

This research will use mice who have a genetic defect that causes the toxic clumps of tau seen in people with dementia. Previous work has shown that adding healthy astrocytes to the mice can prevent the death of neurons. This effect was mirrored when nerve cells with toxic tau were grown in a dish - adding astrocytes stopped the nerve cells from dying. 

The researchers have identified 200 potential 'supporting factors' that astrocytes produce that could be helping nerve cells to survive. The researchers will understand which of these factors are most important for keeping neurons healthy and discover why astrocytes in mice with toxic tau have lost these factors. The researchers will understand whether any of these factors alone can help the neurons to survive. They will also use nerve cells that have been 'reprogrammed' from adult skin cells in people to understand whether the situation is the same in people as in mice.

How will this benefit people with dementia?

The death of nerve cells in people with dementia leads to symptoms such as memory loss, confusion or problems with speech. This project aims to understand whether there is a way that nerve cell death can be prevented using supporting factors from astrocytes. This could open to the door to investigations into potential treatments that could prolong the health of nerve cells in people with dementia. 

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