Investigating how connections between brain cells are lost in dementia

Lead Investigator: Dr Tara Spires-Jones

Institution: University of Edinburgh

Grant type: Project Grant

Duration: 36 months

Amount: £286,988

Scientific Title: Synaptic Proteins that engage Amyloid Beta in the human brain

Why did we fund this project?

Comments from members of our Research Network:

'I support this project because the applicant has developed the technology for examining brain synapses herself and because of the unique availability of the brain bank of donated brain samples for this type of research.'

'This project could provide developments in knowledge and understanding of the processes which cause AD'

'This is an interesting proposal with clear, worthwhile objectives based on a sound hypothesis.'

What do we already know?

Synapses are the connections between brain cells and are essential for the cells to survive. In Alzheimer's disease the synapses do not function properly, leading to the death of brain cells and causing symptoms such as memory loss. Loss of synapses is believed to be one of the strongest early indicators that someone is affected by dementia.

One of the key hallmarks of Alzheimer's disease is clumps of the protein amyloid. These clumps are known to accumulate at synapses in the brains of mice. The presence of amyloid appears to stop the synapses from functioning but the mechanisms that drive this are so far unknown.

What does this project involve?

This project aims to find out what causes the amyloid protein to accumulate at synapses and to discover whether amyloid drives the processes that cause synapses to stop functioning. Dr Spires-Jones and her team will use a technique developed in their lab called array tomography to look at synapses in detail. They will use specially prepared brain tissue that was donated by people who were affected by dementia.

The researchers will see if there are proteins present in the synapses that are driving amyloid accumulation to this area. They will then look for changes at the molecular level that could shed light on the processes leading to loss of synapses.

How will this benefit people with dementia?

Understanding the changes that occur in the brain due to dementia - especially in the earliest stages - is essential to finding new treatments for the condition. This project will use innovative techniques to answer some of the key questions about how the hallmarks of dementia affect brain cells.