ApoE4 gene causes blood-brain barrier degradation

Thursday 17 May 2012

Scientists from various universities have been investigating why the ApoE4 gene makes people more prone to developing Alzheimer’s disease. People who carry two copies of the gene have roughly eight to ten times the risk of getting Alzheimer's disease than people who do not. The researchers determined that ApoE4 works through cyclophilin A (CyPA), a protein found in intracellular fluid.

The presence of ApoE4 causes CyPA to accumulate in large amounts in the cells that help maintain the blood-brain barrier. ApoE4 creates a cascade of molecular signaling that weakens the barrier, causing blood vessels to become leaky. This makes it more likely that toxic substances will leak from the vessels into the brain, damaging neurons and reducing blood flow.

Dr. Robert Bell, researcher at the University of Rochester, said: "We are beginning to understand much more about how ApoE4 may be contributing to Alzheimer's disease. In the presence of ApoE4, increased CyPA causes a breakdown of the cells lining the blood vessels in Alzheimer's disease in the same way it does in cardiovascular disease or abdominal aneurysm. This establishes a new vascular target to fight Alzheimer's disease."

The research team consisted of scientists from the University of Rochester (New York), the University of Southern California, Washington University School of Medicine and the Karolinska Institutet in Sweden. The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging.

www.nature.com/nature/journal/vaop/ncurrent/full/nature11087.html