Jefferson scientists uncover new evidence to help explain statins' effects in Alzheimer's disease

Scientists at Jefferson Medical College and the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia have taken another step in understanding the potential effects of anti-cholesterol drugs on Alzheimer's disease. They have identified a biochemical pathway that affects the activity of statins, particularly their ability to break down an early form of the protein amyloid that clusters and forms sticky plaques in the Alzheimer's brain.

The results may eventually help provide new targets for anti-amyloid drugs to help treat Alzheimer's disease.

Some epidemiological studies have found a link between people taking statin drugs to lower blood cholesterol and a lower incidence of Alzheimer's. Statins work by inhibiting an enzyme involved in cholesterol production, and currently are being tested in clinical trials for their possible effects in slowing the progression of Alzheimer's.

In a series of experiments, Steve Pedrini, Ph.D., a postdoctoral fellow in Neurology in Jefferson Medical College of Thomas Jefferson University and in the Farber Institute for Neurosciences at Jefferson, and his co-workers found evidence suggesting that an enzymatic pathway called Rho/ROCK may play an important role in the metabolism of APP, which is an early form of amyloid, and in turn, the ability of statins to break down a form of APP.

Dr. Pedrini presents his results October 25, 2004, at the annual meeting of the Society for Neuroscience in San Diego. "It's particularly important to understand the pathways involved in Alzheimer's, especially to find more specific therapies," Dr. Pedrini says.

"This reveals an unsuspected pathway linking statins and amyloid metabolism," says Sam Gandy, M.D., Ph.D., director of the Farber Institute for Neurosciences. "This may help unravel statin action in Alzheimer's as well as point the way toward novel anti-amyloid drugs."



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