Two new approaches for treating Alzheimer's disease

An international team of scientists has found a way to restore the nerve cell connections 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 long thought to have caused the disease, providing a new understanding of Alzheimer’s disease and a new approach to ultimately treating it.

Professor Bryce Vissel from St Vincent’s Hospital Sydney, who led the international team, 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,” Vissel said. “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 team’s discovery, as described in the journal Molecular Neurodegeneration, was the identification of a new process that regulates the connections between brain cells, known as ‘RNA editing’. As explained by Vissel, “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.

“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.”

Separate to this, a team led by the Centenary Institute has discovered a connection between the health of blood vessels and the development of Alzheimer’s disease. Their findings, published in the journal GeroScience, suggest that early interventions aimed at improving blood vessel health could lead to new treatments for Alzheimer’s disease.

Dr Ka Ka Ting, the lead author of the study and a researcher in the Centenary Institute’s Healthy Ageing Centre, explained that specific blood vessel cells, called endothelial and perivascular cells, play a crucial role in the forming of the blood–brain barrier, a shield guarding the brain against inflammatory molecules and toxic substances in the bloodstream. “Issues can arise if the barrier becomes permeable, ‘leaking’ these toxins into the brain,” Ting said.

The researchers noticed the presence of senescent blood vessel cells in both Alzheimer’s patients and mouse models of Alzheimer’s; senescent cells are aged cells that have lost their ability to divide and function properly. Significantly, the team found a notable increase in the number of senescent blood vessel cells in and around the blood–brain barrier and linked with areas of leak during the development of Alzheimer’s in mouse models.

“We believe these non-functioning blood vessel cells weaken the barrier, making it more susceptible to inflammatory and toxic substances — potentially exacerbating Alzheimer’s symptoms as the disease advances,” Ting said.

Based on their discoveries, the researchers believe that early intervention targeting blood vessel health could hold promise for Alzheimer’s treatment. This could involve developing medications that specifically target senescent cells of the blood–brain barrier.

“Our study provides a new perspective on Alzheimer’s and the intricate relationship with brain–blood vessels, offering a promising new path for therapeutic approaches aimed at treating this disease,” Ting said.

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