Study Reveals How Alzheimer's Protein Gets From Bloodsteam to Brain

Scientists have discovered how the toxic protein amyloid beta enters the brain to thwart the brain's elaborate filter system and destroy brain cells, according to a study reported in the July 1 issue of Nature Medicine.

"For more than a decade we've known that this protein wreaks havoc in the brains of Alzheimer's patients, but we haven't known how it gets there or how to prevent it from getting there," said study author Dr. Berislav Zlokovic of the University of Rochester Medical Center. "This study answers both of those basic questions, and opens an entirely new avenue for the treatment of Alzheimer's disease."

Using mice genetically engineered to develop Alzheimer's disease, Zlokovic and his colleagues found that amyloid beta accumulated in the brain at eight times the rate of healthy mice as a larger molecule, called RAGE, that ferries amyloid beta from the blood stream to the brain went into overdrive. Normally, RAGE is produced in small amounts by the cells that form the blood-brain barrier.

RAGE is nontoxic and moves unfettered from the blood stream into the brain. Zlokovic and his colleagues found that amyloid beta protein molecules cannot flow through the blood-brain barrier without hitching a ride on the larger RAGE molecules.

When the researchers gave the mice a drug that blocked the process, flow of the protein into the brain was virtually halted and existing accumulations of it in the brain plummeted by more than 70 percent.

"The experiments in this study revealed a great deal of new information about Alzheimer's disease," said Zlokovic. "First, it is now very clear that the body regulates the movement of amyloid beta proteins across the blood-brain barrier. Second, we've shown that that we can use a drug to stop the flow of amyloid beta from the blood to the brain. Finally, we learned that when we block the flow of amyloid beta over time, the brain substantially rids itself of amyloid beta and the amyloid plaques shrink dramatically.

"For patients with Alzheimer's disease, these findings suggest that we can develop a new class of drugs that works by blocking the flow of the toxic Alzheimer's protein into the brain," said Zlokovic.

Other sources: University of Rochester Medical Center