Sep 5, 2013
07:20 AM
The Connecticut Story

Yale Discovery Could Lead to Alzheimer’s Drug, Restored Memory

Yale Discovery Could Lead to Alzheimer’s Drug, Restored Memory

New Haven Register

Stephen Strittmatter

A step in the neurological pathway to developing Alzheimer’s disease has been discovered by researchers at the Yale School of Medicine, and its destructive work may be easily blocked.

Disabling this particular protein in mice with brain damage that mimics Alzheimer’s actually restored memory, the researchers found. The discovery could ultimately lead to an Alzheimer’s drug, researchers say.

It is well-known that amyloid-beta peptides, a string of amino acids that are found in low levels in everyone’s body, can sometimes “clump up in enormous balls that are called plaques,” which are “bigger than cells,” said Dr. Stephen Strittmatter, professor of neurology and senior author of the study published Wednesday in the journal Neuron.

These plaques are common in the brains of Alzheimer’s patients.

But in people who are destined to develop Alzheimer’s, these peptides come together in smaller bodies, Strittmatter said.

“Between the single (amyloid-beta peptide) molecule and these enormous aggregates (plaques), a few molecules come together … as one of the first steps in the disease process,” he said. These smaller groups of cells are called amyloid-beta peptide oligomers, which are “thought to be toxic to neurons. The oligomers make neurons sick,” he said.

What the oligomer does is attach to a protein on the surface of a neuron, and somehow “transmits a signal to the inside of the neuron that triggers this biochemical cascade that goes on to impair synapses,” Strittmatter said.

What the researchers sought was the protein that carried the message from the oligomer to within the neuron’s cell. That missing link is a protein embedded in the neuron cell’s membrane called metabotropic glutamate receptor 5 or mGluR5. This protein is the pathway between the outside and inside of the cell, allowing the oligomer to start its destructive work, but it “is one that’s very easy to make drugs against,” Strittmatter said.

When mGluR5 was blocked in the brain-damaged mice, “we could recover memory function and synapses in these Alzheimer’s mice,” he said. And it was blocked by a drug similar to one being developed for Fragile X syndrome, according to a Yale release.

While the oligomers only show up in the blood of those who are destined to develop Alzheimer’s, there is no test to detect them as yet. “I would suggest that that kind of effort makes sense,” Strittmatter said. “It would be a promising avenue for research.” His lab is among those working on detection of the oligomers, he said.

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Yale Discovery Could Lead to Alzheimer’s Drug, Restored Memory

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