In what could be a significant breakthrough in Alzheimer’s disease research, a team comprising Indian and Canadian scientists has identified the shape of the amyloid beta protein that is believed to trigger the disease.

Alzheimer’s is a notoriously little-understood disease in which clumps of proteins bind together and attack the neurons – a person’s brain cells – triggering a series of events that are manifested as the disease. Alzheimer’s is a degenerative disease usually affecting older people and causes a gradual decline in reasoning and thinking skills as well as memory loss.

Investigating the nature of the protein grouping, and its structure has been a key area of research, but it has never been fully understood.

Shaping a cure

A team from the Tata Institute of Fundamental Research in Mumbai, the Indian Institute of Science in Bangalore and the University of Toronto has now found that this protein is likely to be barrel shaped. This has implications for understanding the nature of the protein so as to enable drug development that could eventually lead to a cure.

The research findings were published online on Tuesday night in ACS Nano, a monthly, peer-reviewed journal published by the American Chemical Society.

"Designing something that will drive a wedge into this protein is possible only when you know the shape of the protein," said Sudipta Maiti, a TIFR professor, who along with colleague PK Madhu led the team. "Now we have an idea of the shape."

He said that they were already working with scientists from Mumbai’s Institute of Chemical Technology to design a drug to target this protein. There is right now no cure for the disease, only drugs thought to slow down its progress or target some symptoms.

It is not clear how the proteins, after grouping together and attaching themselves to the membrane of neurons, cause the disease, nor why this grouping of proteins takes place to begin with. The amyloid beta protein occurs naturally in human beings.

“How it damages the brain cells is not clear,” said Maiti. “But it most likely starts by attacking the fat layers on the membrane.”

A new approach

The findings could help either by improving the understanding of how damage to the membrane occurs or by preventing the proteins from coming together and attaching themselves to the membrane in the first place.

The study applied a new approach towards studying the cells – using a method involving laser light and fat-coated silver nano-particles. The team has been working on this problem for the past five years.

The latest findings suggest strongly the shape of the protein is barrel shaped, but the team is continuing work on this to definitively rule out other possibilities.