February 28, 2005
A so-called “traffic jam” in the network of nerves that crisscross the brain may play a role early in the course of Alzheimer’s disease, researchers report. Like cars backed up on a highway, a disruption of nerve signals could impair the free flow of information and materials in the brain and further compromise brain function, scientists speculate, contributing to the progressive memory loss, confusion, and other telltale symptoms of the disease.
Researchers from the Howard Hughes Medical Institute examined mice that had been genetically engineered to develop a disease that resembles Alzheimer’s. They found defects early in the course of the disease, before symptoms of memory loss became apparent. The animals’ “axons,” long structures that are vital for communicating information from one nerve cell to another, became swollen, blocking the movement of proteins and other critical structures vital for proper nerve function. In a vicious cycle, this nerve “traffic jam” appeared to cause an abnormal protein to build up in the brain, choking off and eventually killing healthy nerve cells.
A similar process may occur in people with Alzheimer’s as well. The researchers examined brain sections taken at autopsy from humans with different stages of Alzheimer’s disease. They detected the same kinds of swelling in those samples that they had seen in the mice. Earlier research has also shown that in people with Alzheimer’s, a toxic substance called beta-amyloid builds up in the brain, forming sticky patches called plaque. The brains of Alzheimer’s victims also become clogged with tangles of proteins called tau.
The researchers speculate that nerve “traffic jams” may be one reason why plaques and tangles arise in the brains of those with Alzheimer’s. They theorize that such nerve defects may contribute to certain inherited forms of early-onset Alzheimer’s that strike at a young age. Alzheimer’s disease might also develop spontaneously in people without a known genetic defect, as the transport machinery in their neurons breaks down with age. “A person could have a predisposition to the disease, or it could just be that as time progresses, one person could by chance accumulate these blockages more than another,” said study leader Lawrence Goldstein of the University of California in San Diego. “And randomly, some people would accumulate more than others, enough to cross a critical threshold and tip the scale toward disease.”
The scientists emphasize that further research is needed to confirm these findings and to learn more about what goes wrong in the brain during Alzheimer’s disease. Still, the findings could one day lead to new drugs and therapies that help preserve or restore transport between nerve cells in the brain, helping to restore memory and brain function. They may also lead to improved diagnostic tests that may detect Alzheimer’s in its earliest stages.
The Fisher Center for Alzheimer’s Research Foundation has played a leading role in funding research into Alzheimer’s disease and the brain. Only through continued research can we learn more about what goes wrong in Alzheimer’s disease, and what we can do to treat and cure it. To learn more, visit www.ALZinfo.org.
Stokin, et al.: “Axonopathy and Transport Deficits Early in the Pathogenesis of Alzheimer’s Disease,” Science, February 25, 2005 pages 1282-1288.