Alzheimer's disease: Most detailed image ever of harmful protein in the brain speeds up treatment research

Scientists have come up with the most detailed images ever of the tau protein that aggregates in the brain of patients with Alzheimer's disease, leading to the death of brain cells. This could help speed up the process to find new drugs that target tau in the brain.

Worldwide, about 50 million people live with dementia – the most common type being Alzheimer's disease. These figures are expected to rise as the global population ages. Little is known about what causes the disease and there is currently no cure for it, although some drugs can help manage the symptoms.

Hallmarks of the disease include the build-up of harmful proteins in the brain - amyloid plaques and tau tangles. As people gradually lose brain cells, the symptoms of the disease emerge and get worse with time.

In previous years, scientists have paid more attention to understanding why amyloid plaques build up and to finding drugs to target them.

However, some teams have very recently started looking more closely at the tau proteins, which are believed to be closely related to patients' cognitive symptoms.

"There has been renewed interest in studying tau. For a few years, we have been able to image amyloid in the brain and very recently we have seen similar techniques being used to image tau proteins," Tim Shakespeare, research officer at Alzheimer's Society, told IBTimes UK.

The study published in the journal Nature takes these imaging efforts one step further. Using an innovative imaging technique known as cryo-electron microscopy, which studies samples at very low temperatures, the scientists were able to obtain a detailed image of the molecular structure of tau filaments from the brain of a 74-year-old woman with a confirmed diagnosis of Alzheimer's disease.

Analysing these very high-resolution images, the scientists provide a first detailed description of the distinct helical and straight tau filaments, which may help explain why they form aggregates in the brain.

Looking for a cure

More importantly, these images constitute a great tool for researchers who are looking for treatments for the devastating neurodegenerative disease.

A drug intended to target harmful proteins in the brain works a bit like a key in a lock. It binds to the protein to clear it out of the brain or to pinpoint its exact location. Knowing the structure of tau is like knowing the inside mechanisms of the lock - and it can help researchers design better drugs to fit that lock.

"Because we now know in details the structure of tau, we can now us computational techniques to compare thousands of drugs against that detailed structure of the protein, and see which drug might bind to it well. With such a method, we can test loads of drugs quickly, there is a potential to speed up the process to find new treatments," Shakespeare, who was not involved in the study, added.

"However, it's worth noting that those treatments would be at the very earliest stage. Once they are identified, they would still have to be developed, tested in mice, and then in humans".

It could still be around 20 years before new treatments based on this research arrive on the market. Nevertheless, looking at what happens in the brain of Alzheimer's disease sufferers in such details bridges a crucial gap in our understanding of the disease.

"This is a fantastic piece of work which will help us understand the pathogenesis of Alzheimer's better. It really is a tour de force," John Hardy, professor of neuroscience at UCL, who was not involved with the study, concluded.