Structure of Alzheimer's protein 'cracked'

An international team, led Dr Jose Varghese of CSIRO in Australia, has uncovered the structure of the toxic protein in the brain, known as amyloid beta, that causes Alzheimer's, the most common form of dementia.

Amyloid beta rapidly self-assembles in the brain and builds up to form plaques which are a hallmark of the disease.

It's thought the accumulation of small amyloid beta aggregates and plaques in the brain disrupt connections in hippocampus -- the area of the brain involved in memory, thus causing loss of neuron function and memory loss.

According to the scientists, there is no cure for Alzheimer's disease, but determining the structure of amyloid beta protein is a vital step towards understanding why it aggregates and plaques occur.

"Before we can understand the processes involved in the deterioration of the brain, we must determine the molecular shape of the damaging protein," Director of CSIRO's Preventative Health Flagship, Professor Richard Head said.

"Until now this has proved incredibly difficult because of the protein's propensity to self assemble and clump together," he added.

Using a highly imaginative approach, the team devised a way of capturing the protein in a crystal long enough to enable its analysis through x-ray crystallography, solving one of a number of potential amyloid beta small aggregates that may play a role in the development of Alzheimer's disease.

Dr Varghese said the team was the first to successfully crystallise the part of amyloid beta that forms plaque by fusing it to a shark antibody to prevent clumping.

"This enabled a structure to be resolved to atomic resolution thus providing an insight into the early molecular processes that occur in Alzheimer's disease.

"The discovery of the amyloid beta's structure offers a molecular target for early detection of Alzheimer's and may provide a vital step towards developing a drug to treat the disease," he said.

Team member Professor Colin Masters from University of Melbourne, said the structure of the amyloid beta has been sought for the past 25 years.

"This discovery provides one of many possible structures, but it is a starting point for discovering drugs which might be used to interfere with the accumulation of the amyloid beta in Alzheimer’s disease," Prof Masters said.

The findings have been published in the latest edition of the 'Journal of Neurosciences'.