New findings reveal insight about protein driving dementia after head injury

20 March 2019

Nature letters: Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules

Researchers at the MRC Laboratory of Molecular Biology in Cambridge have found a key molecular difference between Alzheimer’s disease and a form of dementia brought on by head injury. The findings are reported today (Wednesday 20 March) in the scientific journal, Nature Letters.

A build up of misfolded tau protein is a hallmark of Alzheimer’s disease and a number of other brain diseases, including chronic traumatic encephalopathy (CTE). CTE is a form of dementia linked to repetitive blows to the head.

The researchers have discovered that the molecular structure of tau protein that builds up in the brain in CTE is subtly different to that in other brain diseases.

What is chronic traumatic encephalopathy?

Chronic traumatic encephalopathy, or CTE, was first described by an American pathologist, called Harrison Martland. He noticed a combination of movement and thinking problems in former boxers which he originally dubbed “punch drunk” syndrome. The condition has now been linked to other sports that involve head injury, most notably American football.

Researchers have recently identified distinctive patterns in the spread of tau protein through the brain in CTE, but this new research reveals that the detailed structure of the protein.

What did the researchers do?

In this study researchers looked at tau protein in the brains of three people who died with CTE. The brain samples were donated by an ex-American footballer and ex-boxers.

The researchers used powerful microscopes to show the structure of tau in CTE was different from that found in the brains of people with Alzheimer’s disease.

They found that one of the differences between people with CTE and Alzheimer’s was that tau protein in people with CTE had a unique fold in its structure.

What did the experts think?

Dr Carol Routledge, Director of Research from Alzheimer’s Research UK said:

“The link between head injury and dementia is a fascinating, growing area of research and we know one specific type of dementia – chronic traumatic encephalopathy (CTE) – is directly caused by head injuries.

“In this study, researchers used state-of-the-art microscopes and computer tools to generate 3D structures of the tau protein from the brains of three people with CTE.

“Tau is a culprit protein in a number of diseases that cause dementia and this new research is more evidence that unique forms of tau are involved in the different diseases that cause dementia.

“Dr Ben Falcon who conducted this work today (Wednesday 20 March) won the prestigious ‘Rising Star Award’ at Alzheimer’s Research UK’s Conference for his work revealing the structure of the tau protein in diseases like Alzheimer’s.

“Work like this helps build an important picture of how the tau protein acts in different diseases that cause dementia. Understanding the exact structure of these proteins will help researchers to develop more targeted drugs against them, giving us a greater chance to deliver effective treatments for these conditions in future.”