Scientists Learn How Beta Amyloid Gets into Brain

Scientists studying the brains of mice have learned that beta amyloid is carried across the blood-brain barrier and into the brain by a much larger molecule called RAGE. The findings, which have important implications for Alzheimer's disease, were reported in the July 1, 2002, issue of Nature Medicine.

Mounting evidence suggests that most beta amyloid is produced in cells throughout the body and circulates in the blood, but how this toxic protein gets into the brain has remained unknown. Now, researchers at the University of Rochester Medical Center (NY, USA) have found that beta amyloid molecules cannot flow unaided through the blood-brain barrier but are carried across on a much larger nontoxic molecule, called RAGE. Although RAGE is produced in small amounts by the cells forming the blood-brain barrier, researchers found that mice genetically engineered to develop Alzheimer's disease have huge amounts of RAGE, about eight times the normal amount. When RAGE molecules were disabled, transport of the beta amyloid proteins across the blood-brain barrier came to a halt. In addition, a RAGE look-alike called soluble RAGE was found to block the flow of beta amyloid into the brain.

The researchers also found that as RAGE carried increased levels of beta amyloid into the brain, blood flow within the brain was reduced by half. After RAGE was administered to block the process, blood flow returned to normal. This new finding suggests that blood flow to the brain is sharply reduced in Alzheimer's mice. Decreased cerebral blood flow may help account for the confusion and dementia experienced by Alzheimer's patients.

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




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