Lead Investigator: Professor Diane Hanger
Institution: Institute of Psychiatry, King's College London
Grant type: Project grant
Duration: 36 months
Scientific Title: Using a novel model of disease to understand mechanisms underlying the development of human tauopathy
Why did we fund this project?
Comments from members of our Research Network:
'This project builds on previous work and complements other research in this area'
'A valuable project to clarify understanding of tau in Alzheimer's disease'
'This could be an important advance into tau research'
What do we already know?
Tau is an essential protein that maintains the shape of cells and ensures that they communicate effectively with each other. However, in Alzheimer's disease tau forms toxic clumps called tangles in and around the nerve cells in the brain. The tau present in tangles inside nerve cells is abnormal; it is not properly folded and is modified by the addition of a chemical tag called a phosphate tag. So far it is not understood how these tau tangles form or how they damage nerve cells.
The role of tau is most often studied in animals such as mice that have abnormal tau in their brains and show some symptoms of dementia. However, the current animal models used don't always reflect how tau behaves in the brains of people affected by dementia. Some animals have either too much tau in their brains, or they have a different version of tau that is only seen in rare forms of dementia in people. These don't accurately represent what happens in more common forms of dementia, such as Alzheimer's disease.
Researchers have now developed a new mouse model that produces a similar amount of tau in the brain to what is seen in the brains of people with dementia. These mice also have similar symptoms to humans, such as memory loss that gets gradually worse.
What does this project involve?
The researchers will use this new mouse model to investigate what is happening to tau in the brain. They will see how much the tau is altered by the addition of the phosphate tag. The researchers will also look at the tau found at nerve endings (known as synapses) to find out how much there is and how it has been modified. This will help to understand what effect the tau is having on nerve cells.
Alongside these experiments, the team will use donated human brain tissue, including tissue donated to Brains for Dementia Research, to see how much this new mouse model mirrors what is happening in people.
In additional experiments, the group will use the mice to understand how much tau is being released from brain cells. Tau release is normal and happens when the cells are being used, for example when a person is thinking, but too much or too little release of tau may affect the health of these cells.
How will this benefit people with dementia?
This work will help to understand what happens in the lead up to the formation of a key hallmark of Alzheimer's disease - tangles of the tau protein. This will put us in a better position for the development of new and better drugs that could target one of the major underlying causes of the condition.