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New Approach Yields Exciting Results on Origins of Alzheimer’s Disease: Testing of New Drug to Block Alzheimer's Causing Abeta42 Aggregation Underway
Boston -- A new approach developed for studying brain synapses has yielded valuable information about the production of Amyloid-Beta oligomers (clumps of the Abeta peptide) known to play a key role in the onset of Alzheimer’s disease.
Published in the March 17 issue of the Journal of Neuroscience and funded by Cure Alzheimer’s Fund (CAF), the research of Dr. Sam Gandy, Professor in Alzheimer’s disease Research at the Mount Sinai School of Medicine and a member of the CAF research consortium, and his colleagues, could uncover a new lead in the fight for prevention of this devastating disease.
“It is crucial that we understand how Abeta clumping is regulated, especially at the synapse, if we are to learn how to prevent, stop or slow Alzheimer’s pathology. Abeta42 is believed to be the first subtype of the Abeta peptide to oligomerize (clump together), and therefore most harmful to the brain,” Gandy said. “Now that the neurotransmitter receptor, ‘Group II mGluR’, has been identified as a source of Abeta42, we can find ways to reduce Abeta42 generation at the synapse. Lowering levels of Abeta42 would be predicted to hinder formation of poisonous clumps (oligomers).”
Gandy’s new approach is based on the use of isolated intact nerve terminals (synapses) from mice bred specially using human AD genes. Soong Ho Kim, a postdoctoral fellow in Gandy’s lab, has pioneered this approach. The new system aided in isolating a particular receptor at the synapse, known as “Group II Metabotropic Glutamate Receptor” (or mGluR). Group II mGluR selectively controls the formation Abeta42 at the synapse.
Studies have shown Abeta and its variant Abeta42 play a critical role in Alzheimer’s pathology. Previous research backed by CAF has shown that Abeta42 oligomers are formed at the neuronal synapse, a specialized way station where messages pass from one nerve cell to the next cell in the circuit. Disruption of synapses by Abeta42 oligomers is believed to underlie the loss of brain function in AD.
In unrelated work, a neuroscience bio-tech company, in the process of researching anti- depressants, has developed a safe and orally active drug that blocks ‘Group II mGluR’. In light of Gandy’s new discoveries, he and his colleagues are using the new synaptic terminal system to test the drug before moving on to test mice to determine if the drug can block Abeta from aggregating, which could be a leap forward in the search for preventative therapies.
“The development of this innovative approach by Dr. Gandy and his team could open up new doors of research on this devastating disease,” said Tim Armour, President and CEO of Cure Alzheimer’s Fund. “It’s an important step in understanding and ultimately slowing, stopping or even reversing the effects of Alzheimer’s disease.”