Understanding the role of mRNA and tau in recognition memory

Research project: Recognition memory in Alzheimer’s disease: a role for tau and small molecule RNA?

Lead Investigator: Professor Elizabeth Warburton

  • Institution: University of Bristol
  • Grant type: PhD Studentship
  • Duration: 36 months 
  • Amount: £85,000

Why did we fund this research?

Comments from our Research Network volunteers:

This work has importance in contributing to the biochemical puzzle of what is happening before Tau and amyloid levels cause Alzheimer’s disease

Project summary

Tau is one of the toxic proteins involved in Alzheimer’s disease. This project aims to understand how a molecule in the brain called ‘miR-219’ affects memory and the amount of Tau in brain cells.

The researchers will investigate what happens when they increase or decrease the amount of miR-219 in brain cells. In this way, they can find out if miR-219 could reduce the build-up of Tau in the brain and slow down memory decline.

The background

Tau is one of the toxic proteins linked to Alzheimer’s disease. We know from previous research that Tau builds up in the brains of people with Alzheimer’s disease. This build-up leads to loss of brain cells and worsening of people’s thinking and memory skills. One type of memory that gets worse in Alzheimer’s disease is recognition memory – how well people are able to remember things they’ve seen before.

To keep our brains in good working order, these are lots of processes that go on in our brain cells every day. For example, small pieces of genetic code called ‘microRNA’ look after the amount of different proteins in each brain cell. One of these is called ‘miR-219’. It controls the amount of tau protein in each brain cell. 

Some studies have shown that people with Alzheimer’s disease may have less miR-210 in certain parts of their brain. Less miR-219 might in part lead to the build-up of Tau and the worsening of a person’s memory. We need to understand more about what miR-219 does, and how it might be involved in memory.

What does this project involve?

Researchers will use genetic tools to increase or decrease the amount of miR-219 in brain cells.

They will need to do this in several stages to fully understand what role these small piece of genetic code play in both managing amounts of tau in brain cells, and memory. 

As a first step, they will see what happens to tau proteins in an isolated brain cell when they increase or decrease the amount of miR-219. Then using rats, Professor Warburton and her team will test the effect of increasing or decreasing the amount of miR-219. In particular, in a part of the brain linked to recognition memory. These rats will then be tested on different kinds of memory task, for example how well they remember objects they’ve seen before. 

Finally, some rats will have a procedure that causes tau proteins to build up in their brain cells. The amount of miR-219 in their brain will be increased and they will be tested on some memory tasks. The researchers hope they will see the amount of tau protein go down, and an improvement in memory.

How will this project help people with dementia?

We need to understand more about what role these small pieces of genetic code play in memory and controlling proteins like tau. This study will help us learn more about how these processes might work in healthy brains as well as in Alzheimer’s disease.

If we understand how this might lead to Alzheimer’s disease, this gives us the chance to develop treatments to stop the disease in its tracks. Future studies could start to explore how this might also apply to people, and how we might develop a treatment to tackle tau. 

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