Researchers Learn 'Secrets' of Alzheimer's Disease

Published February 27, 2009

| Associated Press

Scientists are unraveling some of the mechanisms behind the plaques in the brain that are a hallmark of Alzheimer's disease, offering new leads for drugs to treat the fatal brain-wasting disease.

A team at Massachusetts General Hospital and Harvard Medical School in Boston reported on Thursday in the journal Science that amyloid plaques agitate a type of brain cell called an astrocyte needed for normal brain function.

On Wednesday, a team at Yale University in New Haven, Connecticut, reported in the journal Nature that prions — proteins known to wreak havoc on the brain in mad cow and Creutzfeldt-Jakob diseases — appear to kick-start the toxic effects of amyloid plaques in Alzheimer's disease.

The findings shed new light on the complex brain mechanisms behind Alzheimer's, which is marked by memory loss, confusion and eventually the inability to care for oneself.

"Alzheimer's disease is probably a very complex disease with many things happening simultaneously," Kishore Kuchibhotla of Harvard said in a telephone interview.

Kuchibhotla's team used an advanced optical imaging technique to study the brains of live mice with Alzheimer's-like plaques. They found astrocytes, a star-shaped type of brain cell needed to support normal brain function, become hyperactive in the presence of amyloid plaques.

"It supports the idea that somehow amyloid beta does something that alters brain function," Kuchibhotla said.

Astrocytes are known to proliferate around injury sites, but in Alzheimer's, astrocytes appear to share this information with other astrocytes in far-flung parts of the brain using a communications pathway known as a calcium-signaling network.

Brian Bacskai of Harvard likens it to a group of bystanders looking at a car wreck. Instead of just watching, astrocytes appear to pull out their cell phones and alert their friends in different areas of the brain, which also become hyperactive.

"This development may prove to be a breakthrough in our understanding of the disease, and the hunt for new Alzheimer's drugs," Rebecca Wood, chief executive of the Alzheimer's Research Trust in Britain, said in a statement.

"Research now needs to identify exactly what effect this hyperactivity is having on the brain," Wood said.

Researchers at Yale, meanwhile, think they are gaining a better understanding of what makes amyloid plaques toxic.

"We have known that amyloid-beta is bad for the brain, but we have not known exactly how amyloid-beta does bad things to neurons," Stephen Strittmatter of Yale School of Medicine said in a statement.

Strittmatter's team found the first step in amyloid beta damage appears to involve prion proteins. These proteins are normally harmless unless they are mangled or misshapen in some way, as in mad cow or Creutzfeldt-Jakob disease.

The Yale team believes short bits of amyloid beta latch onto these prion proteins. "They start the cascade that make neurons sick," Strittmatter said. He thinks this early process would make a good research target for new Alzheimer's drugs.

There is no cure for Alzheimer's, and current drugs merely delay symptoms. It affects 5.2 million people in the United States and 26 million globally, according to the Alzheimer's Association.

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