Toxic particles in the brain which cause dementia could be detected by antibodies

A new antibody, that spots the toxic particles that destroy healthy brain cells in dementia patients, could be used to diagnose and monitor the disease.

Researchers from Cambridge University designed a way to recognise these particles – called amyloid-beta oligomers – which are a hallmark of Alzheimer’s.

The creation of the antibody could lead to the development of new diagnostic treatments to detect Alzheimer’s early on and keep it under control, authors say.

Toxic particles are difficult to spot, researchers say, but this new antibody has a three order a magnitude greater affinity to them – making them easier to track. 

The Cambridge team worked with researchers from University College London (UCL) and Lund University in Sweden to create the new detection antibody.  

Researchers reported in the Proceedings of the National Academy of Sciences that the antibody is highly accurate at detecting toxic oligomers and quantifying them. 

Study leader Professor Michele Vendruscolo, from Cambridge’s Centre for Misfolding Diseases, said this meets an urgent need for quantitative methods to recognise the elusive oligomers.

He said: ‘Through our innovative design strategy, we have now discovered antibodies to recognise these toxic particles.’

Dementia is one of the leading causes of death in the UK, and costs more than £26 billion each year – a figure that is expected to more than double in the next 25 years. 

Estimates put the current annual cost to the global economy at nearly £1 trillion.

Alzheimer’s disease, the most prevalent form of dementia, leads to the death of nerve cells and tissue loss throughout the brain – resulting in memory failure, personality changes and problems carrying out daily activities.

Abnormal clumps of proteins called oligomers have been identified by scientists as the most likely cause of dementia. 

Although normally responsible for important cell processes, these proteins become rogue and kill healthy nerve cells when someone has Alzheimer’s.

Proteins need to be closely regulated to function properly, the team said.

When this quality control process fails, the proteins misfold, starting a chain reaction that leads to the death of brain cells, according to the Cambridge researchers.

Misfolded proteins form abnormal clusters called plaques which build up between brain cells, stopping them from signalling properly.

Dying brain cells also contain tangles, twisted strands of proteins that destroy a vital cell transport system, meaning nutrients and other essential supplies can no longer move through the cells.

Despite more than 400 clinical trials for Alzheimer’s disease taking place, no drug that can modify the course of the disease has been approved. 

Dementia is the only condition in the top 10 causes of death in Britain without a treatment to prevent, stop, or slow its progression.

Professor Vendruscolo said the idea that these particles are the cause of Alzheimer’s is a prevalent view but it has not been fully validated.

This is ‘in part because amyloid-beta oligomers are so difficult to detect, so there are differing opinions on what causes Alzheimer’s disease,’ he said.

‘The discovery of an antibody to accurately target oligomers is, therefore, an important step to monitor the progression of the disease, identify its cause, and eventually keep it under control.’

The lack of a successful way of detecting oligomers has been a significant obstacle that Alzheimer’s research has thus far been unable to overcome.

This has been hindering the development of any kind of effective diagnostic or therapeutic intervention, the team say.

Study first author Dr Francesco Aprile, from Cambridge’s Centre for Misfolding Diseases, said the proteins are difficult to detect, isolate and study.

‘Our method allows the generation of antibody molecules able to target oligomers despite their heterogeneity, and we hope it could be a significant step towards new diagnostic approaches,’ said Aprile.

The scientists were able to design antibodies for antigens that are highly challenging, such as those that live only for a very short time.

they targeted specific regions of the proteins in order to create an antibody that was three times better at spotting them than other previous attempts.

This difference is the key feature that enables the antibody to specifically quantify oligomers in both in vitro and in vivo samples, the team said.

The researchers hope that this tool will enable the discovery of better drug candidates and the design of better clinical trials for people affected by the devastating disease.