Molecule could protect against Alzheimer's disease

Behind the Headlines

Tuesday February 17 2015

People with Alzheimer’s disease develop clumps of protein inside their brain

Alzheimer's disease is most common in people over the age of 65

"Alzheimer's breakthrough: scientists home in on molecule which halts development of disease," The Daily Telegraph reports. The so-called "chaperone molecule", known as "Brichos", helps prevent the clumping of proteins, which can lead to the death of brain cells.

Scientists don't know what causes Alzheimer's disease, but people who have the condition tend to have abnormally high amounts of stringy proteins called amyloid plaques in their brains. The plaques interfere with brain cells, damaging brain function.

News of a molecule that could stop some of this damage is encouraging, but declaring a "breakthough" is premature. We don't know if this molecule has an effect on humans, because the experiments were all carried out on mice.

Although Brichos stopped damage occurring in a specific amyloid-related biological pathway, some of the damage associated with Alzheimer's disease could occur via other routes.

As the researchers point out, Brichos would probably not be a suitable candidate for a drug treatment. Because of its composition, it could be absorbed by the body before it reached the brain.

The hope is that there may be more "chaperone molecules" out there that do have the ability to cross the blood-brain barrier and help prevent brain cell damage.

 

What can I do to prevent Alzheimer's disease?

  • stopping smoking if you smoke
  • cutting down on alcohol if you drink large amounts
  • eating a healthy balanced diet, including at least five portions of fruit and vegetables every day
  • exercising for at least 150 minutes (2 hours and 30 minutes) every week by doing moderate-intensity aerobic activity (such as cycling or fast walking)
  • make sure your blood pressure is checked and controlled through regular health tests
  • if you have diabetes, make sure you keep to the diet and take your medication

Read more about preventing dementia.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge, a trio of Swedish institutions – Karolinska Institutet, Lund University, and the Swedish University of Agricultural Sciences – and Tallinn University in Estonia.

It was funded by several health foundations, charities and research grants from national and international non-commercial organisations. No conflicts of interest were declared.

The study was published in the peer-reviewed science journal, Nature Structural and Molecular Biology.

The UK media's reporting was somewhat overexcited, with most framing the study as a breakthrough, implying that a treatment was inevitable.

Many showed no restraint by failing to talk about the drawbacks of the research, which were outlined by the researchers themselves in their conclusion.

Headlines from The Independent and The Guardian reporting a "possible breakthrough" were the most balanced. The Mirror went bigger, reporting a "Major Alzheimer's breakthrough".

The Mail Online and Daily Telegraph also towed the "breakthrough" line. Arguably, these are all overstatements as there is no guarantee that any of this works when used on humans. At the moment, we only know it works in mice.

Some sources, such as The Times, talked about the possibility of this research leading to a statin-type drug, taken as a preventative measure by people who were free of any dementia-like symptoms. This development is, currently, just speculation.

We also suspect that many people would be reluctant to take such a drug if they were free of any symptoms  a suspicion prompted by the ongoing controversy about statins, and whether the potential benefits outweigh any risk of side effects.

 

What kind of research was this?

This was mainly laboratory research, looking into the complex biological processes involved in Alzheimer's disease.

Alzheimer's disease is the most common type of dementia, affecting almost 500,000 people in the UK. Symptoms of Alzheimer's include progressive loss of mental ability, associated with the gradual death of brain cells.

While the cause is unknown, Alzheimer's disease has been associated with the build-up of proteins called amyloid plaques in the brain.

The researchers say fine fibres (fibrils) that make up the amyloid plaques kick-start toxic reactions around them, which ultimately cause further damage to the surrounding brain cells. The researchers wanted to see if they could stop or lessen this secondary damage.

 

What did the research involve?

The research studied purified amyloid protein fibrils under a variety of controlled conditions in the laboratory. They used these experiments to better understand how the fibrils formed, and how they catalysed other toxic reactions that could be causing damage to brain cells.

They also tested a short protein section (a molecule of amino acids) called Brichos to see if it could interfere with the processes they were seeing, and lessen the damage.

Experiments used lab-grown human cells, as well as mouse brain tissue.

None of the experiments investigated whether Brichos could prevent symptoms of dementia or Alzheimer's in mice or people. It was looking at chemical reactions, not symptoms.

 

What were the basic results?

The Brichos protein stopped reactions caused by the amyloid fibrils, reducing their toxicity in mice brain cells.

The experiments showed that Brichos did this by binding to the surfaces of amyloid fibrils. This specific binding stopped the toxic chain reactions that usually lead to damaging aggregation of other proteins. In essence, some of the disease process had been stopped.

 

How did the researchers interpret the results?

The authors summarised: "These results reveal that molecular chaperones [like Brichos] can help maintain protein homeostasis by selectively suppressing critical microscopic steps within the complex reaction pathways responsible for the toxic effects of protein misfolding and aggregation."

They said Brichos was just the first protein they had investigated, and there may be other molecules that work in a similar way.

 

Conclusion

This study showed that a molecule called Brichos can selectively block some of the toxic effects linked to the accumulation of amyloid protein in the brains of mice. The research on Brichos is at a very early stage, having only been tested in mice.

Dr Laura Phipps of Alzheimer's Research UK says: "This study has revealed clues on how to block one important chain of events in the disease." Dr Doug Brown of the Alzheimer's Society added: "This revelation is exciting, as it gives scientists a whole new way of looking at the problem, opening the doors to possible new treatments."

Contrast this with the Mail Online outlining that this discovery "raises the prospect of a treatment which could be routinely taken in middle age to stop dementia. It could even result in a pill that could be used to treat dementia in the same way that statins are used to prevent heart disease today".

While the Mail's vision – among other news sources – is certainly possible, it is premature. There is no guarantee this research will lead to effective treatments for Alzheimer's disease.

And it should also be noted this study has limitations, which should be considered.

Brichos stopped secondary damage occurring in a specific amyloid-related disease pathway. But damage could occur by other means. And it doesn't appear to reverse existing damage.

Most people with Alzheimer's disease are diagnosed when they already have significant damage to their brain that has caused symptoms severe enough to affect their daily lives. So any "treatment" would need to be taken before symptoms appear, thereby acting as more of a prevention.

Similarly, as Brichos doesn't stop the amyloid plaques forming, it is unlikely to be fully preventative. There may also be side effects when using Brichos on people. It is also likely that Brichos will be absorbed by the body before it reaches the brain.

All these issues and many more will need to be ironed out by further research.

This study is certainly a step in the right direction, because it improves our understanding of the biology of Alzheimer's disease. But it is too early to say whether Brichos will lead to useful treatments or preventative medicines in the future.

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

Analysis by Bazian

Edited by NHS Choices

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Alzheimer's: Stan's story

Stan Lintern has had Alzheimer’s disease for 10 years. He is cared for by his wife Denise, who helped set up the Maidstone branch of the Alzheimer’s Society and runs the helpline. Last year, she was awarded an MBE for services to her local community.

Media last reviewed: 03/05/2016

Next review due: 03/05/2018

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