How is blood flow linked to Alzheimer’s disease?

Rachel Harris is a PhD student with Prof Seth Love and Dr Shelley Allen at the University of Bristol. She’s interested in the role of blood flow in dementia.

In dementia, we know that what is good for the heart is good for the head and that keeping blood vessels healthy can help protect the brain and lower dementia risk. However, we’re yet to understand all the processes that link the vascular system and nerve cell health. Through my PhD, I hope to reveal more about the connection by studying a group of proteins which ‘talk to’ both nerve cells and blood vessels.

Alzheimer’s disease and vascular dementia are the two leading causes of dementia. Sometimes Alzheimer’s disease is seen with vascular dementia –part of what’s known as mixed dementia. We think that Alzheimer’s disease, mixed dementia and vascular dementia are not always entirely separate diseases, but are on a spectrum. Researchers are working hard to understand more about the similarities and differences, as this will improve diagnosis and treatment.

Vascular disease – which can often precede coronary heart disease or stroke – and dementia, share common risk factors, including high blood pressure, high cholesterol and smoking. Some researchers also found evidence of direct links between Alzheimer’s disease and the vascular system.

In vascular dementia the brain doesn’t receive enough blood, and therefore oxygen, which results in nerve cell death. We also know that blood flow to the brain is reduced in patients with Alzheimer’s disease and this may be part of the reason nerve cells are dying in this form of dementia too.

In Alzheimer’s disease, clumps of a protein called amyloid form around nerve cells in the brain. Amyloid also builds up inside the walls of brain blood vessels. This amyloid damages blood vessels and may interfere with blood flow in the brain. You can learn more about amyloid in blood vessels from our blog from the Alzheimer’s Research UK Conference earlier this year.

My research group previously found that a protein, known as vascular endothelial growth factor (VEGF), is expressed at higher levels in the brain of people with Alzheimer’s disease when we compare to the brains of healthy people of the same age. This protein is made all over the body and is switched on when there is not enough oxygen getting to the cells. In the lab we are trying to understand how this particular protein affects the brain in Alzheimer’s disease.

To do this, we are using brains donated for dementia research via the South West Dementia Brain Bank, a Brains for Dementia Research centre and part of the UK Brain Bank Network. We are also able to grow nerve cells in controlled conditions and then investigate the molecular chain of events going on inside cells. This helps us to understand how the changes we see in the human brains happen.

Right now we’re looking at how VEGF communicates with cells in the brain. It does this by sticking to receptors on the surface of nerve cells, brain support cells called astrocytes and blood vessels. Here are some pictures of nerve cells and blood vessels that are stained for these receptors.

Human brain tissue ‘stained’ to look for the proteins we’re interested in – they are expressed on brain support cells, blood vessels and nerve cells.

We hope that by understanding the pathways that lead to reduced blood flow to the brain in Alzheimer’s disease and vascular dementia we can develop new and effective treatments for the two biggest causes of dementia.

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• Read more about the work in Prof Love’s laboratory into improving detection of vascular dementia.