How toxic various sizes of Alzheimer's clusters can be to brain's nerve cells

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Washington, August 12 (ANI): In a breakthrough that may pave the way for an effective treatment for Alzheimer's disease, scientists at the University of California-Los Angeles (UCLA) have created various sizes of clusters in their lab, which exactly match the clusters of the amyloid ß-protein (Aß) protein that form in the brains of those affected with the disease.

The researchers say that their work has shown that the ability of these grape-like clusters to kill nerve cells in the brain, scientifically known as toxicity, increases dramatically as they increase in size.

They say that though the larger clusters are more toxic than smaller ones, the larger formations are relatively rare.

Given that smaller versions are numerous, the researchers say, they are an inviting target for the development of new therapeutic drugs.

"We now have the best understanding yet of what types of toxic A-beta structures we should target with new classes of therapeutic drugs," said senior author David Teplow, a professor of Neurology at UCLA.

The researchers have found that the larger the cluster, the greater the toxicity, but they also found that the increase in toxicity with these clusters is not linear.

"Clusters that contain two Aß molecules are more toxic than a single Aß molecule, and those with three molecules are more toxic that those with two," said Teplow.

He pointed out that clusters composed of two Aß molecules are three-fold more toxic than the simple monomer compound, but those made of three molecules and four four molecules are more than 10-fold more toxic than are monomers.

This suggests that the larger, more toxic clusters should be the target for scientists trying to stop Alzheimer's.

But Teplow notes that the relative amounts of the smaller clusters are far greater than that of the bigger clusters, and are, in total, more toxic.

So in an Alzheimer's brain, the larger clusters are relatively rare, he said.

"Think of the molecules being wrapped in very weak Velcro. So a number of molecules can bind together to form large clusters, but they break apart very easily," he said.

Having developed a process in the lab to be able to make pure forms of these Aß clusters of specific size will enable detailed study of their structures to show where every atom is.

"This will make development of drugs much easier and likely more successful," he said. (ANI)

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