Understanding the relationship between the internal structure of the brain and Alzheimer’s disease

Research project: Correlating local complexity of the extracellular space of the brain with clearance efficiency of amyloidogenic oligomers.

Lead Investigator: Dr Juan Varela 

  • Institution: University of Cambridge 
  • Grant type: PhD
  • Duration: 36 months 
  • Amount: £84, 981

Why did we fund this research?

Comments from our Research Network volunteers:

This is a difficult, complex, and ambitious project, but if successful could have a leading beneficial effect on research.

Project summary

The human brain is a complicated network of many different types of cell. In between these cells exists extracellular space which makes up approximately 20% of the brain. In Alzheimer’s disease, amyloid plaques build up in the extracellular space.

This project aims to understand how the structure of the extracellular space might make influence amyloid build up. They will also explore the role these extracellular spaces play in helping clear toxins from the brain. 

The background 

Alzheimer’s disease is the most common type of dementia, and yet researchers are still working hard to understand how it causes the brain’s cells to get sick and die.

One of the hallmarks of Alzheimer’s disease are the build up of plaques around the brain cells, which are made up of a specific protein called amyloid. These plaques are thought to be toxic, however how they damage brain cells is still unknown. 

The brain is made up of a network of millions of different cells, each with distinct roles.

Even though the cells are packed together to make up the brain, there is still space surrounding the cells, which is referred to as extracellular space. These spaces make up approximately 20% of the brain.

It is also in these spaces where the amyloid plaques in Alzheimer’s disease form. The relationship between this extracellular space in the brain and the build up of amyloid is yet to be fully explored. This is due to the fact that in the past is has been difficult for researchers to examine these tiny extracellular spaces within the brain. 

What does this project involve?

This project aims to understand the role the extracellular space plays in Alzheimer’s disease in more detail. To do this, the researchers will use cutting edge imaging techniques to visualise the brains of rats, where special fluorescent nanoparticles make the extracellular spaces in the brain visible. The researchers hope to use this technique to identify “cul-de-sacs” in the extracellular space; dead ends where toxic proteins might me more likely to build up. 

The researchers want to understand whether these “cul-de-sacs” are more prone to amyloid plaque build up than other areas of the extracellular space. The researchers will then go on to explore the role these extracellular spaces in the brain play in clearing toxic amyloid from the brain. 

How will this project help people with dementia?

This project uses new, innovative techniques to explore an aspect of the human brain we have not been able to investigate in detail previously. The data from this project will go on to inform larger studies to help us further understand the causes of Alzheimer’s disease.

The extracellular space also presents a new target for future therapies, especially if it is found to have a role in clearing the brain of toxic proteins like amyloid. This research not only helps us understand more about Alzheimer’s disease but also presents new potential opportunities to develop drugs to treat it. 

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