Molecule removes Alzheimer's plaques from brains of mice

Behind the Headlines

Wednesday December 9 2015

The mice were genetically engineered to have Alzheimer’s like symptoms

Treated mice performed better in maze tests

"A molecule can clear Alzheimer's plaques from the brains of mice and improve learning and memory, Korean scientists have found in early tests," BBC News reports. However, the Daily Express’s claims of a "wonder pill" are premature.

One of the defining characteristics of Alzheimer’s disease is the formation of abnormal clumps of protein in the brain, known as amyloid plaques. It's debatable whether these plaques cause the symptoms of Alzheimer's, or are themselves a symptom of an underlying pathology.

Scientists tested a chemical called EPPS on mice that had been genetically engineered to contract a disease similar to Alzheimer's in humans from five months of age. The researchers found that the amount of plaques characteristic in the brain had been reduced in the treated mice.

Treated mice also did better in tests designed to measure their memory and learning skills than mice that had been given plain drinking water.

This may tentatively suggest that the plaques do play some sort of role in the symptoms of Alzheimer's.

Obviously, the standard caveats of assuming that results in animals will be replicated in humans apply to this study, and EPPS may well turn out to be ineffective or unsafe in humans.

That said, there are reasons for cautious optimism, and in the words of Dr Frances Edwards, Reader in Neurophysiology at University College London, "this could be a very interesting drug indeed".

 

Where did the story come from?

The study was carried out by researchers from the Korea Institute of Science and Technology, and GoshenBiotech Inc, and was funded by the Korea Institute of Science and Technology. The study was published in the peer-reviewed science journal Nature Communications on an open-access basis, so it is free to read online.

Most of the media coverage was accurate and responsible, and included comments from experts warning that animal studies often do not translate into treatments of use in humans.

However, some of the headline writers exaggerated the implications of the research, which could arguably give people affected by Alzheimer's false hope. 

 

What kind of research was this?

This was an experimental animal study using mice. Animal studies are used right at the start of a drug development process, to discover its effects before testing on humans.

 

What did the research involve?

Researchers used genetically-modified mice that had already got signs of memory and learning problems. 

The mice were given water laced with a molecule called 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS) – at two different doses – and others plain water, for three months. The mice were then tested again for memory and learning problems. The researchers looked at their brains for signs of the amyloid plaques characteristic of Alzheimer's disease.

The mice's memory and learning abilities were tested using mazes. The researchers also carried out studies of toxicity, by feeding mice increasingly high amounts of EPPS, and tested the effect of EPPS on amyloid plaques in petri dishes or test tubes, to try to see exactly what the EPPS was doing to the plaques.

The researchers compared the results from the treated and untreated genetically-modified mice. They also compared their results with normal mice that had not been modified to get Alzheimer's disease, to see whether it had any additional effect.

In a further study, mice had amyloid proteins injected into the brain, either before or at the same time as being given two weeks' worth of EPPS, to see whether the chemical could prevent memory problems.

 

What were the basic results?

Genetically-modified mice treated with EPPS did better on some short-term memory and learning tests than genetically-modified mice that had not been treated, although not as well as normal mice. 

The genetically-modified mice had fewer amyloid plaques in their brains. The improvement in memory and learning tests was more marked in mice fed higher doses of EPPS.

The laboratory work showed that EPPS seemed to "disaggregate" or dissolve the clumps of amyloid protein that forms the plaques, breaking them down into smaller molecules. The researchers said this reduced the amount of inflammation in brain tissue.

There was no effect on the normal mice treated with EPPS, suggesting the substance only improves memory and learning ability for mice designed to get Alzheimer's disease.

The mice injected with amyloid proteins and given EPPS did not develop the memory problems seen in mice injected with the proteins, but not treated.

 

How did the researchers interpret the results?

The researchers were cautious about their results. They said: "Additional studies are warranted to determine whether these favourable actions of EPPS and derivatives will translate into a therapy that might potentially be useful across a range of AD [Alzheimer's disease] stages."

 

Conclusion

The authors of this small study are right to be cautious about the results. The brains of mice and humans are very different, and we don’t know from this study whether the chemical EPPS would have a beneficial effect on people with Alzheimer's disease in the same way it seems to affect mice.

While the exact mechanism of Alzheimer's disease is unknown, some think that amyloid plaques in the brain cause inflammation and damage to the brain tissue, resulting in memory and cognitive problems. 

This study adds to the theory that amyloid plaques are a cause of the symptoms of Alzheimer's disease, rather than a result of the disease.

Existing treatments for Alzheimer's disease can, in some cases, slow the progress of the disease, but they cannot cure or reverse it. The results of this study are interesting to scientists, who have long wanted to find a treatment that not only prevents the build-up of new amyloid plaques, but dissolves existing plaques. While the treatment seems to have done that for this group of genetically-modified mice, we don't know if it would have the same effect on humans.  

Analysis by Bazian. Edited by NHS Choices. Follow NHS Choices on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

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Brain tour: what is dementia?

Dementia affects over 800,000 people in the UK. It is not a disease in its own right and it is not a natural part of ageing. It is an umbrella term that describes a group of symptoms that are caused by many diseases that affect the brain for example, Alzheimer's disease.

Media last reviewed: 20/02/2015

Next review due: 20/02/2017

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