Live brain cell test reveals protein link to Alzheimer’s
Scientists using living human brain tissue have shown for the first time how a toxic form of a protein linked to Alzheimer’s can stick to and damage the connections between brain cells.
Small pieces of healthy human brain tissue – collected during routine neurosurgery operations – were exposed to the protein, known as amyloid beta.
Unlike when subjected to a normal form of the protein, the brain tissue did not attempt to repair damage caused by the toxic form of amyloid beta, experts say.
The study also found that even small changes in the natural levels of amyloid beta – either increasing or decreasing – were enough to disrupt brain cells. This suggests the brain requires a finely tuned ‘sweet spot’ of the protein to function properly, experts say.
Treatment hope
Researchers at the University of Edinburgh hope the discoveries will allow them to hone in on drugs that have the best chance of preventing the loss of synapses – connections which allow the flow of messages between brain cells and are vital to healthy brain function.
Alzheimer’s disease attacks synapses and their loss strongly predicts reduced memory and thinking abilities.
We believe this tool could help accelerate findings from the lab into patients, bringing us one step closer to a world free from the heartbreak of dementia. These findings are a testament to the incredible support of my funders and the hard work of my team members Dr Robert McGeachan and Dr Soraya Meftah who led on the experiments.
Dr Claire Durrant
RAD Dyson Fellow and UK DRI Emerging Leader at the Centre for Discovery Brain Sciences at the University of Edinburgh
Living tissue
Central to the early success of the Dyson RAD Dementia Research Acceleration Project has been the pioneering method that keeps tiny fragments of human brain alive in laboratory dishes for several weeks after collection, with the patient’s permission.
This innovative approach offers a rare and powerful opportunity to investigate the early stages of Alzheimer’s disease in living human brain cells.
Researchers also discovered that brain slices taken from the temporal lobe, a region known to be affected early in Alzheimer’s, released higher levels of another key disease protein, called tau. This may help explain why this part of the brain is particularly vulnerable in the early stages of the condition, as increased tau release may enable faster spread of toxic forms of this protein between cells.
Early insights
In addition, a number of the samples were found to contain early indicators of Alzheimer’s, such as amyloid plaques and tau tangles, demonstrating the potential of this model to study the disease before symptoms appear.
Experts say this innovative approach will make it easier to test experimental drugs before they enter clinical trials, increasing the chance of finding drugs that work in the human brain.
It’s a horrendous reality that as things stand, one in three people born today, will die with dementia. Someone develops dementia every three seconds – and we still don’t have a cure. I created Race Against Dementia to challenge this awful disease in the fullest sense. Our collaboration across industries allows us to think keener and faster and the breakthrough that we have achieved shows what is possible when science moves faster, with new tools and fresh thinking. Our unique program is enabling us to test potential treatments which are bringing us closer to a world without dementia. I am sure that for you, like me, that cannot happen soon enough.
Sir Jackie Stewart OBE
Founder of Race Against Dementia, which has supported Dr Durrant’s laboratory since 2019
Industry partners
The study is published in Nature Communications and was supported by a fellowship from Race Against Dementia (RAD) – a charity formed by Sir Jackie Stewart following his wife’s dementia diagnosis – and a £1 million donation from the James Dyson Foundation – Sir James Dyson’s charity that supports medical research and engineering education. The donation helped employ two scientists, secure time from research nurses, and obtain the cutting-edge laboratory equipment needed for working with living human brain tissue.
The project links experts from Formula One and Dyson with early-career researchers to accelerate progress towards a cure for dementia. It marries best practice from these fast-paced, innovative industries with novel scientific techniques to investigate the biology of human brain tissue.
I’ve been delighted to support Dr Durrant's novel approach. Working with brain surgeons and their consenting patients nationwide to collect samples of living human brain and keep them alive in the lab is a groundbreaking method. It allows researchers to better examine Alzheimer's disease on real human brain cells rather than relying on animal substitutes, such as mice. Dr Durrant’s findings show that she is progressing towards solving one of the most devastating problems of our time.
Sir James Dyson
Founder of Dyson
This important work by Dr Durrant’s team brings a new tool to scientists’ toolbox to better understand Alzheimer’s disease and how to treat it. The use of living human tissue samples generously donated by people undergoing surgery to remove brain tumours allows scientists to probe how living human brain reacts to toxic proteins produced in Alzheimer’s, and in future will allow testing of whether new treatments are effective in human brain. This cutting-edge study is an example of how the UK Dementia Research Institute is at the forefront of global efforts to understand and treat Alzheimer’s.
Professor Tara Spires-Jones
Group Leader at the UK Dementia Research Institute at the University of Edinburgh
