Exploring the waste disposal system in brain cells and what it means for Alzheimer’s disease and Frontotemporal dementia

Lead Investigator: Dr Gemma Lace

• Institution: University of Salford
• Grant type: PhD Studentship
• Duration: 36 months
• Amount: £84,176

Why did we fund this research?

Comment from one of our Research Network volunteers:

'Addressing the issues with the build-up of toxic proteins and the failures of the systems that should clear them, appears to offer a good route to finding ways to slow down or perhaps even stop degeneration.'

Project summary

What causes the different diseases of the brain that lead to dementia are still not fully understood. It’s thought that in some types of dementia, the waste disposal system within brain cells might not work properly.

This project will examine this waste disposal system in brain cells with Alzheimer’s disease and frontotemporal dementia, to try and better understand what is causing disease in the brain cells and how it might spread from cell to cell. 

The background 

Through research we know that some of the diseases that cause dementia, such as Alzheimer’s disease and frontotemporal dementia are characterised by abnormal build ups of different proteins in the brain. These plaques are thought to be toxic and cause brain cells to become sick and die, leading to dementia. It is also thought that this damage can be “spread” from brain cell to brain cell, although the way this spread happens is yet to be understood.

Cells, including those in the brain have built in waste disposal systems that are able to break down proteins that have been made incorrectly or are no longer needed. However, there’s evidence that in some types of dementia like Alzheimer’s disease and frontotemporal dementia, this waste disposal system isn’t working correctly. It’s thought that the waste disposal system that is affected differs between different types of dementia. 

What does this project involve? 

This project will try to understand more about how problems with the waste disposal system in brain cells might lead to certain types of dementia.

It will also try to understand how these problems might lead to disease spreading from brain cell to brain cell. To do this the researchers will examine microscopic packages called exosomes, which can be passed from one cell to another.

Exosomes can contain proteins or DNA. They can also contain molecules of miRNA, which can act as a switch inside a cell, turning certain processes (like waste disposal) on or off. Although researchers believe that problems with waste disposal and brain cell to brain cell spread of disease are both important in how dementia progresses, the relationship between the two has yet to be explored. 

The researchers will first look at human brain tissue from the Manchester Brain Bank and compare the different miRNA they find in brains from people who have lived with Alzheimer’s disease and with frontotemporal dementia. They will then investigate the relationship between miRNA and the brain cell waste disposal system, using drugs that increase or decrease waste disposal respectively. 

How will this project help people with dementia? 

Diagnosing the different types of dementia, like Alzheimer’s disease or frontotemporal dementia, quickly and non-invasively still remains a challenge.

Understanding more about the difference between the different causes of dementia helps develop improved methods of dementia diagnosis. In particularly, this project could help to identify new markers in the body which could be used to help diagnose exactly what type of dementia a patient has. Being able to detect dementia sooner and more accurately in turn ensures that patients receive the correct treatment. 

The more we understand about the causes of dementia and what is actually going wrong within the brain, the more information we have to design the new treatments of the future.

By exploring the waste disposal system in brain cells and understanding the role it plays in Alzheimer’s disease and frontotemporal dementia, researchers can identify new drug targets. This will help them design new drugs for dementia, which could be the treatments of the future.