Thursday, 28 September 2023

 World-first discovery to prevent memory loss among people living with Alzheimer’s

Researchers at St Vincent’s Hospital in Sydney have achieved a breakthrough in our understanding of dementia and a new way forward in its treatment. Through their discovery, the team restored nerve cell connections (synapses) in the brain that are destroyed by Alzheimer’s and which are thought to store memory. 

The team essentially rescued memory without having to remove any of the protein clumps (beta-amyloid) long thought to have caused the disease. 

The study provides a new understanding of Alzheimer's disease and a new approach to ultimately treating it. 

St Vincent’s Sydney’s Professor Bryce Vissel – the leader of the international team of scientists behind the discovery – said that microscopic nerve cell connections in the brain, known as synapses, are thought to be essential to memory formation, although this is not yet proven.

“People living with Alzheimer’s experience a loss of nerve cell connections which has been speculated to cause the debilitating loss of memory that is synonymous with the disease,” said Professor Vissel.

“Our research set out to answer the question: by rescuing these connections, can we rescue memory?

“We now have compelling evidence, in a model of Alzheimer’s, that preventing the breakdown in these synapses is possible. 

“This in turn rescues memory, offering a new way forward to understanding and treating the disease.”

The key to the discovery – set to be published this week in the world leading neurology journal Molecular Neurodegeneration – was the identification of a new process that regulates the connections between brain cells, known as ‘RNA editing’. 

“RNA editing can be used as a 'molecular switch'. By flicking the switch in the mice models we use in our research we were able to stop the brain cell connections from breaking down. 

“Remarkably, we discovered that by doing so we restored lost memory in the mice. 

“For many years people have been focusing on removing amyloid (a build-up of protein) from the brain as a pathway to an Alzheimer’s cure but without any success.

“We found RNA editing worked to restore nerve cell connections without having to remove any amyloid from the animals' brains resulting in the return of memory. 

“Dementia is now the number one cause of death of women in Australia. There are no cures. 

“Having shown that preventing synapse loss offers a way forward to treating Alzheimer’s, our team will now accelerate work towards developing an effective treatment for this devastating disease,” Prof Vissel said.

Professor Bryce Vissel is available for interview.  

Media contact: Nikki Potent 0407 013 616

Scientific statement:  The novel scientific discovery is that a process called RNA editing, that regulates a receptor called the AMPA receptor subtype GluA2, in turn regulates synapse (more specifically, dendritic spine) loss in the Alzheimer’s brain.   The team discovered that by ‘forcing’ the editing of the receptor, they could recue the synapses in an Alzheimer’s model, thus restoring memory.  The research is the first to show that synapses are regulated by RNA editing and that reduced RNA editing in Alzheimer’s disease leads to synapse loss. This ground-breaking research not only offers hope for a new approach to AD treatments, but also sheds novel light on the intricate mechanisms that govern memory more generally.

This work was made possible by a dedicated international team of researchers: Amanda L. Wright, Lyndsey M. Konen, Bruce G. Mockett, Gary P. Morris, Anurag Singh, Lisseth Estefania Burbano, Luke Milham, Monica Hoang, Raphael Zinn, Rose Chesworth, Richard P. Tan, Gordon A. Royle, Ian Clark, Steven Petrou, Wickliffe C. Abraham and Bryce Vissel.