Study May One Day Resolve Alzheimer's Debate
Finding sheds light on molecular mechanisms of the disease
(HealthDay is the new name for HealthScoutNews.)
MONDAY, July 28, 2003 (HealthDayNews) -- New research has provided a possible way to settle the long-running debate about the molecular causes of Alzheimer's disease.
Two things happen on the molecular level as the disease slowly destroys intellectual power. Tangles of a protein called tau form inside dying brain cells. And plaques composed of protein fragments called beta-amyloid form outside those cells. There have been arguments, often testy, about which molecular event is of primary importance in the pathology of Alzheimer's.
Now, two researchers at Northwestern University report a direct relationship between those two molecular processes -- a discovery that could eventually lead to an effective therapy for a condition that is now virtually untreatable.
That connection centers on a family of enzymes called caspases, which promote cell suicide, says Dr. Vincent L. Cryns, an associate professor of medicine at Northwestern's Feinberg School of Medicine. He is part of a team reporting the discovery in the July 28-Aug. 1 issue of the Proceedings of the National Academy of Sciences.
Recent research has shown that beta-amyloid activates caspases, and this latest study uncovered what happens next.
"We have shown that exposing neurons [brain cells] to caspases causes caspases to cut a piece off the tau protein," Cryns says. "The shorter version of tau assembles into tangles much more rapidly than the normal version. So we have shown a connection between the two major brain abnormalities that occur in Alzheimer's disease."
That finding could be "directly relevant to patients," he says. Cryns and Lester A. Binder, a professor of cell and molecular biology at Northwestern, have created antibodies that zero in on the shortened version of tau. "We showed that these antibodies detect tangles in Alzheimer's brains," Cryns says.
The finding suggests that inhibiting caspases would be a possible future therapy, he says. "But that is not easy to do. How you would get a drug into the brain is one problem. Then there would be possible side effects of inhibiting caspases, which are important in their own right," he adds.
A cautious assessment by Bill Thies, vice president for medical and scientific research at the Alzheimer's Foundation, is that "because this is a basic science paper, its importance may only be established years in the future."
But the finding can help researchers working to develop new treatments, he adds. "A lot of people have been looking at ways to limit amyloid," Thies says. "If it turns out that amyloid is triggering tau that is an important place where we might be able to intervene."
Binder and Cryns say they now will try to establish the timing of tau cleavage in Alzheimer's disease and to determine the exact role tau cleavage plays in the death of brain cells.
This work, they write, "will provide a common ground between the amyloid and tau proponents and point to the need to consider both of these interrelated pathological events in future studies and therapies."
To get the latest information on research and treatment, consult the Alzheimer's Association or the National Institute of Neurological Disorders and Stroke.