How Organ Systems Outside the Brain May Affect Alzheimer's

One of the primary characteristics of Alzheimer’s is the accumulation of a molecule called amyloid-beta (A-beta), which is believed to be toxic to neurons and many other brain cells.

In Alzheimer’s, A-beta accumulates to form toxic plaques that disrupt normal brain function. Researchers believe that finding ways to clear A-beta may be a key to treatment or prevention of Alzheimer's.

A study published in the Journal of Alzheimer's Disease provides new insights into the way A-beta in the peripheral blood stream affects A-beta clearance in the brain.

Scientists found that elevated A-beta levels in the blood stream of rats resulted in A-beta being eliminated from the brain more slowly. These results clearly demonstrate that freely circulating A-beta concentrations outside the brain can regulate A-beta clearance rates inside the central nervous system.

Researchers are coming to understand that the brain does not act alone in the task of clearing A-beta. It can be shuttled back and forth between compartments inside the brain and the peripheral blood supply where A-beta interacts with other organ systems.

Treatments that increase the flow of A-beta away from the brain hold great therapeutic promise. Despite the promise of such work many basic questions still need to be answered about how the brain interacts with the rest of body to hold A-beta in check.

Dr. David Cook of the University of Washington School of Medicine commented, "Answering this seemingly simple question has been problematic because it can be very difficult to control A-beta concentrations in the blood. We knew from previous work that the liver plays an important role in removing A-beta from the blood. So, we thought if we temporarily prevented liver-mediated clearance it might be possible to set or 'clamp' peripheral A-beta levels long enough to find out whether A-beta in the blood stream affects A-beta clearance from the brain. We were a bit surprised to see how effective this strategy was. Peripheral A-beta clearance immediately halted almost completely. For several years it has been suggested that the circulatory system can act like an A-beta sink. The data clearly show that the liver is the primary drain."

Hepatology expert, Dr. Sum Lee remarked, "The liver influences virtually everything that happens in the body, so it is not far-fetched to imagine that in the future it may be possible to find ways to help the brains of Alzheimer's patients with their livers."

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References:
1. Marcos A. Marques, J. Jacob Kulstad, Christopher E. Savard, Pattie S. Green, Sum P. Lee, Suzanne Craft, G. Stennis Watson, and David G. Cook. Peripheral amyloid-beta levels regulate amyloid-beta clearance from the central nervous system. Journal of Alzheimer's Disease 16:2.