The results may eventually help provide new targets for anti-amyloid drugs to help treat Alzheimer's disease. They report their findings Jan. 11, 2005 in the online journal the Public Library of Science Medicine.
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 is being tested in clinical trials for their possible effects in slowing the progression of Alzheimer's.
In a series of experiments, Sam Gandy, M.D., Ph.D., director of the Farber Institute for Neurosciences at Jefferson, Steve Pedrini, Ph.D., a postdoctoral fellow in Neurology in Jefferson Medical College of Thomas Jefferson University and in the Farber Institute for Neurosciences and their co-workers found evidence suggesting that an enzymatic pathway called Rho/ROCK may play an important role in the metabolism of APP (amyloid-beta peptide precursor protein), which is an early form of amyloid, and in turn, the ability of statins to break down a form of APP.
According to Dr. Gandy, APP can be broken down in two ways: "Bad cleavage" releases toxic amyloid-beta; "good cleavage" destroys it. Evidence shows that when the pathway ROCK1 is active, less good cleavage occurs. Statins, however, reduce ROCK1 activity, making it more likely that good cleavage will be in effect.
"It's particularly important to understand the pathways