Alzheimer's investigators at Gladstone find a drug target for guarding memories

Building on research into the way in which glial cells called astrocytes store memories, a group of investigators at the Gladstone Institutes has zeroed in on a particular target--A2A adenosine receptors--that could play a role in preventing one of the most devastating symptoms of Alzheimer's.

These star-shaped cells teem in the brain, supporting the memories we store throughout our lives. Adenosine receptors on astrocytes proliferate in the brains of Alzheimer's, the scientists found. And blocking them appeared to heighten the memory capacity of mice used in an animal study designed to test their theory.

While there was no difference in learning ability between two groups of mouse models for the disease designed with normal or reduced levels of A2A receptors in astrocytes, the population with fewer adenosine receptors was found to have better memories. And they were able to detect a memory effect on mouse models which carried the amyloid beta plaques many believe--but aren't certain--cause this disease.

There are existing therapies that are known to block these receptors, and now the team wants to start testing them in humans to see if they can be repurposed to fight Alzheimer's, a disease that has attracted billions in research funds.

Caffeine is already known to play a role in the way that astrocytes function, supporting a hunch that coffee might help in delaying the disease.

"Given the many roles of astrocytes in the brain, one might expect a global disruption of brain function," says lead author Anna Orr, a staff scientist at Gladstone. "Instead, we see a very specific effect on memory retention."

Lennart Mucke

"Our findings have provided us not only with a new perspective on the role of astrocytes in cognition, but also with an exciting drug target to enhance memory and maybe even stave off memory decline in Alzheimer's disease," says senior author Dr. Lennart Mucke, director of the Gladstone Institute of Neurological Disease and professor of neurology and neuroscience at the University of California, San Francisco. "Next, we will explore the therapeutic implications of our discovery by repurposing available drugs that block these adenosine receptors and are well tolerated in humans."

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