Research team identifies cause of memory loss

Identification may lead to drug development targeted to dementia

A research team that included members from The Johns Hopkins University and the University of Minnesota Medical School has for the first time identified a substance in the brain that is proven to cause memory loss. This identification gives drug developers a target for creating drugs to treat memory loss in patients with dementia.

Karen H. Ashe of the University of Minnesota Medical School led the research team, which is publishing its results in the March 16 issue of Nature. The team included Michela Gallagher, Krieger-Eisenhower Professor and chair of the Department of Psychological and Brain Sciences at Johns Hopkins, and Ming T. Koh, a post-doctoral fellow.

“Now that we have found a protein complex that causes cognitive decline and loss of memory, we will be able to aim our investigations not only to learning how that substance is implicated in disease, but also toward prevention,” Gallagher said.

More specifically, once the memory-robbing protein complex is better understood, drugs could be developed to stop Alzheimer’s disease in its tracks, the researchers say.

Currently about 4.5 million Americans live with Alzheimer’s disease, a number that is expected to rise to 14 million over the next two decades.

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 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. Thus, it is often difficult to discern whether people are experiencing the normal memory impairment that comes with aging or if they are, in fact, 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 even before nerve cells begin to die. To test that hypothesis, the team 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. They extracted and purified this newly found protein complex and injected it into healthy rats. The rats suffered cognitive impairment, confirming that this protein has a detrimental effect on memory.

Researchers at the University of Southern California and the University of California, Irvine, also collaborated on the research.