Scientists make key Alzheimer's finding

cientists have discovered the process by which mice normally sweep away the protein forming the brain tissue plaques that are a hallmark of Alzheimer's disease. The findings point to blood circulation in the brain as a key player in preventing the beta amyloid plaques that speckle the brains of Alzheimer's patients. The new information should help researchers better understand how these plaques accumulate and perhaps how to prevent them.

In a study in mice, a team led by Medical Center neurosurgeon Berislav Zlokovic found that blood vessels are responsible for removing the beta amyloid protein in healthy brain tissue. Zlokovic's team found that the endothelial cells that line the blood vessels are key to the process. In particular, a protein known as LRP-1--a molecule that plays a role in the transport and metabolism of lipids such as cholesterol--rapidly shuttles beta amyloid out of the brain and across the blood-brain barrier to the body, which breaks it down into harmless waste products.

Zlokovic

Amyloid deposits in the brain are one of the classic signs of Alzheimer's disease. Most scientists agree the deposits are toxic to brain cells, causing the neurodegenerative damage seen in Alzheimer's patients, while some believe the deposits are a byproduct of a more basic disease process. Either way, neurons die, and removing plaques or preventing their formation is a line of research pursued by many physicians and scientists.

Zlokovic's team injected amyloid peptide into the brains of mice, blocked various molecules in the bloodstream, then monitored the blood to see how well the proteins were being removed from the brain. They found that when LRP-1 was blocked, the removal of amyloid from the brain slowed dramatically. They also showed that healthy middle-aged mice 9 to 12 months old had fewer LRP-1 molecules in their blood vessels, and that these mice shuttled amyloid out of their brains at only half the rate of young mice.

The results mark the first time scientists have shown that the vascular system has a role in removing plaques from the brain. Zlokovic says it's likely that amyloid peptide is constantly present in the brain but that in healthy young animals and people, blood vessels constantly remove it, ferrying it away from the brain cells that it can damage.

"The idea that healthy people have small amounts of amyloid peptide in their brains, and that somehow the body is constantly neutralizing it, has been around for awhile," says Zlokovic. "But just how the body takes care of it has been a big question mark." Scientists have known that neurons themselves can clear small amounts of amyloid from the brain, but Zlokovic says blood vessels remove the protein 50 to 100 times faster, doing in just half an hour what takes neurons days to remove. It's the fastest known handling of amyloid by any molecule or process in the body.

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