Researchers Reveal Clues To Alzheimer’s Brain ‘Plaques’

A team of researchers from the University of Michigan has revealed clues to how amyloid plaques may form in the brain of people with Alzheimer’s. Understanding the mechanism leading to the formation of amyloid plaques could allow researchers to develop new ways to try to stop this process. The research is published on 17 March in the journal Proceedings of the National Academy of Sciences (PNAS).

One of the hallmark features of Alzheimer’s disease is the abnormal clumping of a protein called amyloid into plaques inside the brain. First noticed over 100 years ago by Alois Alzheimer, amyloid plaques have long been implicated as a contributor to the death of nerve cells in the brain in the disease.

To understand more about what could cause amyloid plaques to form in the brain, researchers at Ann Arbor used cells and mice in the laboratory to mimic changes in Alzheimer’s. Their findings suggest that part of the cell called the ‘Golgi apparatus’ could play an important role.

The Golgi apparatus is a transport hub of the cell – sorting and packaging molecules and sending them on to different parts of the cell. The amyloid protein itself normally traffics through the Golgi during its production. The team studied how this process was affected in cells and mice developed to have a genetic change that causes high levels of amyloid to be made – similar to that seen in the human disease.

The researchers found that abnormal amyloid build-up in these cells caused the Golgi to break into fragments. This fragmentation of the Golgi kick-started a negative chain of events which accelerated the production and trafficking of even more amyloid through the Golgi. The authors believe this could contribute to the development of amyloid plaques.

The team identified two proteins, cdk5 and GRASP65, which appear to play a role in the breakdown of the Golgi. Blocking these two proteins in the lab prevented the Golgi from breaking down and caused less amyloid to be produced. The research highlights this mechanism as a potential target for treatments aimed at stopping the formation of amyloid plaques.

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:
“Over recent years we have seen large efforts in the research community to understand amyloid plaques in Alzheimer’s and develop ways to stop them building up. This early research identifies a chain of events that may be involved in the formation of amyloid plaques in mice, but further research will be needed to confirm whether it plays a role in people.

“Clinical trials are already underway with experimental treatments aimed at stopping amyloid build-up in Alzheimer’s. The results of ongoing clinical trials will show whether targeting amyloid could be a successful strategy for treating the disease. In the meantime we must continue to translate research findings into the clinic, to give new treatments the best chance of success. Drug discovery initiatives, including those being pioneering by Alzheimer’s Research UK, are providing funding and support to speed up the development of new treatments for people with dementia.”