August 6, 2004
Using specialized immune system proteins to treat the plaques and tangles that clog the brain in Alzheimer's disease, investigators from the University of California at Irvine have uncovered new clues to the devastating memory-robbing illness. Although the research was conducted in mice, it illustrates the importance of the kind of basic scientific research that may one day lead to effective new treatments against Alzheimer's disease in people as well.
The researchers used immune system proteins called antibodies that attack a toxic substance in the brain called beta amyloid. Beta amyloid builds up in the brains of those with Alzheimer's disease, forming sticky patches called plaques and interfering with brain circuits critical for learning and memory. Many researchers believe it is an underlying cause of the devastating illness.
When the scientists injected the antibodies into mice, beta amyloid plaques in the brain disappeared, as did amyloid deposits within brain cells. What's more, treatment that rid the brain of plaques also helped to rid the brain of the potentially damaging tangles formed by another protein called tau. Normally, tau forms structures in the brain that help provide nourishment to brain cells. But in Alzheimer's disease, the tau protein forms thread-like deposits within brain cells, called neurofibrillary tangles. The researchers concluded that beta amyloid might lead to the development of tau tangles in those with Alzheimer's disease.
This new information suggests a cause-and-effect link between two of the major hallmarks of Alzheimer's disease: plaques and tangles. Although most scientists believe that beta amyloid is responsible for producing much of the brain-damaging effects of Alzheimer's disease, many scientists believe that tangles also represent a feature that contributes to the illness. The significance of the new research findings is that now scientists see a link between beta-amyloid and tangles. As a result, it is possible that therapies aimed at lowering beta-amyloid might then also eliminate neurofibrillary tangles.
As Alzheimer's progresses, the brains of affected people become increasingly filled with plaques and tangles. Researchers are hopeful that immune-based therapies, such as those used here, may lead to ways to clear the brain of these damaging substances. Scientists are also researching various experimental drugs and other treatments in the search for a cure. In fact, in the present study, a drug that lowers beta-amyloid was used, and that too resulted in cleared tangles, at least for those in the earlier stages of the illness. In addition to plaques and tangles, many additional factors likely contribute to Alzheimer's disease. Inflammation, for example, has been implicated in damage to the brain and other organs. Genes and environmental factors also play a role in Alzheimer's.
Basic scientific research is vital for unraveling the underlying causes of Alzheimer's disease. Only then can scientists be empowered to develop effective therapies, by rationally targeting the disease-causing mechanics of the brain. Research sponsored by organizations like the Fisher Center for Alzheimer's Research Foundation is critical for funding studies that may one day lead to effective new treatments for the disease.
Salvatore Oddo, Lauren Billings, J. Patrick Kesslak, David H. Cribbs, Frank M. LaFerla: "Ab Immunotherapy Leads to Clearance of Early, but Not Late, Hyperphosphorylated Tau Aggregates via the Proteasome." Neuron, Volume 43, Number 3, August 5, 2004, pages 321-332.