Researchers try to unknot Alzheimer's protein tangles

July 07, 2017 394

"Abnormal deposits that build up in the brain during Alzheimer’s have been pictured in unprecedented detail by UK scientists," reports BBC News.

Alzheimer’s disease is characterised by two proteins that take abnormal forms and build up in the brain: beta amyloid plaques and tangles of tau protein, both of which are thought to contribute to the symptoms of Alzheimer’s.

Recent drug research has focused on amyloid plaques, but without much success. Interest is now shifting to tau tangles.

Researchers used a new ultra-magnifying technique called cryo-electron microscopy to picture tangles of tau protein in detail.

Cryo-electron microscopy involves freezing a tissue sample (which helps preserve it) and then using powerful microscopes to study the sample at a molecular level.

From this, researchers produced models of the molecules in the protein fibres. Eventually, this work may lead to therapies that can prevent the fibres spreading.

But that’s not going to be easy. Brain cells need tau protein to function. The key will be to prevent overgrowth of tau protein fibres without stopping tau carrying out its vital work.

Any drug that targets tau would need to get inside brain cells. One expert estimates it may take 10-15 years before new drugs could be developed from this starting point.

So, this is just the start – but it’s a good start. As well as Alzheimer’s disease, tau is implicated in several neurological diseases, including Parkinson’s disease, so other patients may also benefit from this advance.

Where did the story come from?

The study was carried out by researchers from the Medical Research Council Laboratory of Molecular Biology in Cambridge in the UK, and Indiana University School of Medicine in the US.

It was funded by the UK Medical Research Council, the European Union, the US National Institutes of Health, and Indiana University School of Medicine.

The study was published in the peer-reviewed journal Nature.

BBC News carried a balanced and accurate report of the study findings, but failed to spell out how much work now needs to be done before any new treatments can be developed.

What kind of research was this?

This pathology study used donated brain tissue, which was processed and underwent imaging to examine its protein structure.

This type of study is important for advancing our understanding of disease. It doesn’t automatically lead to a cure.

What did the research involve?

Researchers used brain tissue donated by the family of a woman who died of Alzheimer’s disease 10 years after diagnosis, aged 74. The tissue was processed to extract fibres of purified tau protein.

These were spread across a carbon grid, frozen, and hundreds of images taken using an electron microscope.

The researchers used the images to describe the molecular structure of the protein fibres and create 3-D molecular models of them.

They also carried out other analysis of the tau fibres, such as checking whether they could "seed" growth of the protein fibres in cultured cells, and compared them with other Alzheimer’s disease brain cell samples.

What were the basic results?

Researchers found two types of tau fibres: a straight filament and a paired helical (spiral-shaped) filament.

The detailed molecular maps of the filaments show an ordered c-shaped core, common to both types of fibre. This core seemed to be necessary to seed the fibres through cultured brain cells.

The core is attached to what researchers describe as a "fuzzy coat", which doesn’t have any clear molecular order and may grow randomly from the core.

The results were corroborated by other tests, which they said were "in good agreement" with proteins found in earlier research and mass spectrometry imaging of 10 other cases of Alzheimer’s disease.

How did the researchers interpret the results?

The researchers said the structures they identified "establish a basis for understanding the differences between molecular conformers of tau aggregates [build-ups]".

They say the research "opens up new possibilities for studying the molecular mechanisms underlying a wide range of neurodegenerative disease".

Conclusion

There’s a tendency when scientists announce a breakthrough in our understanding of a disease to immediately start thinking about whether this could lead to a cure.

While the ultimate aim of research into Alzheimer’s disease is of course to be able to prevent or treat it, early research like this is more about understanding the disease mechanisms.

This piece of research demonstrates how a new technique can be used to identify the molecular structure of abnormal protein deposits in the brain. That’s a big step forward for use of this technology, which may be useful for other diseases, too.

The causes of Alzheimer’s disease still aren’t well understood. The brain is complex. Tangles of tau protein may be an important part of the development of Alzheimer’s disease – but we don’t know whether stopping the spread of tau tangles would halt the memory problems and mental decline characteristic of the disease.

While we can celebrate this advance as a scientific breakthrough in our understanding of Alzheimer’s disease, we need to be patient about the chances of a cure.

Until then, while there’s no guaranteed way of preventing Alzheimer’s, the following may help lower your risk of developing the condition:

stopping smoking
not drinking large amounts of alcohol
eating a healthy, balanced diet, including at least five portions of fruit and vegetables every day
exercising for at least 150 minutes (2.5 hours) every week
staying mentally active

Read more about how to prevent Alzheimer’s.