Researchers Identify Cause Of Memory Loss; Identification May Lead To Targeted Drug Development For Dementia

The research, led by Professor of Neurology Karen H. Ashe, M.D., Ph.D., will be published in the March 16, 2006, issue of Nature.

"Finding the specific cause of memory loss and cognitive decline gives scientists a protein complex to target," Ashe said. "Now we can begin to work on how that protein leads to the disease and what we can do to prevent it from harming the brain."

Once the memory-robbing protein complex is better understood, drugs could be developed to stop Alzheimer's disease in its tracks. Currently about 4.5 million Americans live with Alzheimer's disease, a number that is projected to increase to 14 million in the next 20 years.

In the past, it was generally accepted that Alzheimer's disease was caused by plaques and tangles, unnatural accumulations of two naturally occurring proteins in the brain: amyloid-beta, which builds into plaques between nerve cells in the brain; and tau, which forms the tangles bundles inside nerve cells.

Ashe's lab proved last year that the tangles are not the cause of memory loss; this latest research shows the plaques aren't a major cause either.

People with Alzheimer's disease exhibit memory impairment before they are formally diagnosed, or before nerve cells in their brains begin to die. Often it can be difficult to tell whether people are experiencing the normal memory impairment that comes with aging or if they are in the early stages of Alzheimer's disease.

The researchers hypothesized that there was a substance in the brain that causes memory decline that is present before the nerve cells die. The researchers used mice whose genetic makeup was manipulated to develop memory loss much in a way people develop subtle memory problems before the earliest stages of Alzheimer's disease. Using mice that showed early signs of memory loss and had no plaques or nerve cell loss in the brain, they discovered a form of the amyloid-beta protein that is distinct from plaques. Once extracted and purified, the newly found protein complex was injected into healthy rats. It triggered cognitive impairment in the tested animals, confirming the detrimental effect of this protein on memory.

Ashe's research was done in collaboration with scientists at Johns Hopkins University, University of Southern California, and University of California, Irvine.