Why do we need this project?
Dementia is the loss of mental ability due to the gradual death of brain cells. Vascular dementia is the second most common type of dementia. It's estimated to account for about 20% of all cases of dementia, which itself affects around 850,000 people in the UK. It's more common in men and usually starts before the age of 75.
The development of vascular dementia is attributed to a lack of a blood supply to the brain. This is generally caused by cerebral small vessel disease (SVD), which is damage to the blood vessels to the brain and which leads to changes deep in the brain, including tiny strokes.
SVD also results in bleeding in the brain. During a person’s life, signs of vascular dementia and SVD can show up as characteristic features on brain scans, including small vessel changes and bleeds in the grey matter of the brain, accumulation of fluid in the white matter of the brain and enlargement of spaces around the blood vessels. The exact cause of these changes is not known and it is therefore difficult to identify a target for treatment.
Apart from providing blood to feed the brain, the arteries also have a very important function in removing the fluid waste from the brain. Professor Carare’s team have demonstrated that the elimination of waste from the brain is along tiny channels embedded in the walls of arteries, and this fails in the ageing grey matter. These channels are called “basement membranes”, as they form the base upon which other cells are layered. Basement membranes are formed by networks of proteins and they are anchored to the cells. One important anchoring molecule is ‘alpha-dystrobrevin’.
What is the aim of this project?
In this project, the aim is to demonstrate that failure of drainage of fluid from the grey and white matter of the brain is a mechanism underlying SVD.
What will happen during the project?
In order to test the elimination of fluid from living systems with disturbed basement membranes, two types of genetically modified mice will be used.
Read our Animal Research Position Statement.
What is the intended outcome of the project?
The outcome of this research should provide us with the elements of failed drainage and elimination of fluid from the brains with SVD, understanding what is in this fluid could then enable the development of efficient treatments to treat SVD caused through this underlying mechanism.
36 months (start date: TBC)