Investigating how tau tangles spread between brain cells in dementia

Research project: Analysis of tau release from cells in exosomes: potential role in the spread of tau pathology

Lead Investigator: Dr J. Mark Cooper
Institution: Institute of Neurology, University College London
Grant type: PhD studentship
Duration: 3 years
Amount: £91,000
Scientific Title:

Why did we fund this project?

Comments from members of our Research Network:

'Looks like well thought out and possibly promising research that could lead on to development options for treatments in the future.'

'I feel this would benefit people with dementia as if we can stop the transmission of tau between cells or understand this process we are one step closer to identifying a disease modifying treatment.'

'A well thought through project, with clear, useful goals and good support for the student.'

What do we already know?

The protein tau is essential for brain cells to work properly. However, in people affected by Alzheimer's disease and other types of dementia, tau forms clumps called tangles. The tangles prevent the brain cells from working properly. There is clear evidence thattau tangles spread within the brains of people affected by dementia as the disease develops. 

The researchers behind this project believe that the tangled tau can leave affected cells in little packets known as exosomes. These exosomes travel to nearby cells and deliver their contents into the new cell. The researchers are investigating how proteins become packaged into exosomes and are released from cells. They believe that the tangled tau uses this system to leave one cell and enter another. This project will determine whether tau tangles using this mechanism can cause tau to clump in other cells. This could explain how the tau tangles spread throughout the brain in Alzheimer's disease.

The lead researcher, Dr Mark Cooper, has previously investigated whether a protein called alpha-synuclein also uses exosomes. Alpha-synuclein can lead to damage to brain cells if it does not behave as expected. It is particularly associated with Parkinson's disease and dementia with Lewy Bodies. This research discovered that alpha-synuclein can use exosomes to exit cells. The new project will use many of the same techniques to determine if tau also uses this mechanism.

What does this project involve?

The project is a collaboration between several different groups within the Institute of Neurology at UCL. It will concentrate on the use of cells grown in the laboratory to investigate specific features of the protein tau.

The aim is to understand how and why tangled tau enters exosomes and is released from cells. The research will also focus on whether it is this mechanism that causes tau to tangle in nearby cells. It will allow the researchers to understand better how the tau tangles spread in Alzheimer's disease and other forms of dementia. 

Benefit to the lives of people affected by dementia

This project will improve our understanding of how the protein spreads within the brains of people affected by dementia. The researchers hope to create a cell model to illustrate this process. They are hoping that this model can be further developed in mice to give a clearer idea of how the mechanism functions.

If successful, the cell and mouse models could be used to screen and test potential therapies to stop the tau tangles from spreading. This method may find a treatment that could help to stop dementia in its tracks.

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