Further investigating the role of blood flow to the brain and risk of dementia

Lead Investigator: Professor Karen Horsburgh

Institution: University of Edinburgh 

Grant type: Project

Duration: 36 months

Amount: £326,594

Scientific Title: Mechanisms leading to neurovascular dysfunction and cognitive impairment: role of NADPH

Why did we fund this project?

Comments from members of our Research Network:

'The focus on identifying the causal mechanisms in the development of AD is important and offers practical application in the future.'

'I think the long term benefits of this research could be huge'

'I feel this is a very different way of looking at a common aspect of Alzheimers and should be investigated further.'

What do we already know?

As well as the hallmark amyloid and tau proteins, problems with blood flow to the brain are thought to be a major contributor to the development of Alzheimer's disease andvascular dementia. A reduction in blood flow can lead to brain cells being starved of the oxygen and nutrients that they need. This can cause the brain cells to die, which leads to symptoms of dementia. However, the mechanisms that cause reduction in blood flow are so far unclear.

There is evidence that the cells forming the blood vessel lining could be damaged with age and due to conditions such as high blood pressure, diabetes and high cholesterol. This injury is thought to be caused by an increase in molecules called NADPH oxidases. The Alzheimer's-related amyloid protein is also thought to increase the levels of NADPH oxidases. So far it is unclear whether decreased blood flow can lead to changes in the levels of these molecules and therefore damage to the blood vessels. 

What does this project involve?

The researchers aim to investigate whether reduced blood flow leads to an increase in both amyloid levels and NADPH oxidases and whether this process is linked to developing memory problems. 

They will build on previous work using mice that have low blood flow to investigate the effect that this has on the brain. This project will focus more on the role of NADPH oxidases and their relationship with the amyloid protein and see if together they have an effect on blood vessels. The researchers will also see if blocking the levels of NADPH oxidases may be a potential target for future treatments for dementia.  

How will this benefit people with dementia?

Vascular dementia and Alzheimer's disease are the most common forms of dementia, but there are no treatments for either condition. Understanding the factors that lead to one or both of the conditions gives us a clearer idea of the causes and will allow researchers to find potential targets for future treatments.