Of mice, memory, and molecules
In 1984 scientists found that the main ingredient in the Alzheimer plaque is a minuscule protein fragment called amyloid-beta, or Aß. Since then, scientists have learned how these fragments assemble themselves into small clusters and then into larger structures that eventually form plaques. Evidence suggests that the small clusters of Aß may be the real suspects in the pathology of Alzheimer's disease.
Sylvain Lesné, Ph.D., a postdoctoral fellow in Ashe's lab, identified a number of these Ab clusters in the brains of the Alzheimer-like mice. Ashe's group then assessed which of these suspects were at the scene of the crime — or which of them were abundant when the Alzheimer-like mice first began having memory problems.
The evidence pointed to Aß*. When researchers injected Aß* into healthy rats, the memory-impairing agents were caught red-handed. The rats experienced memory loss like the symptoms observed in the mouse models of Alzheimer's disease.
Perhaps the most intriguing outcome of Ashe's study is the hope for correcting memory problems. The memory impairment observed in the rats was reversible and occurred long before the brain was permanently damaged.
You really have to attack this disease at the basic levelto understand it at the molecular level. Then you have a real chance to intervene.— Timothy Ebner, M.D., Ph.D., head of the Department of Neuroscience
"Aß* is acting like an intoxicant," says Ashe, "putting the neurons to sleep but not killing them."
The implications of this discovery are profound. "If we can intervene before nerve cells are irreversibly damaged or dead, that would be a tremendous advance," says Sam Gandy, M.D., Ph.D., a neurologist and molecular biologist at Thomas Jefferson University and chair of the Alzheimer's Association's Medical and Scientific Advisory Council.
"At the moment," explains Gandy, "we're only intervening after there are clear clinical signs and symptoms, which so far have been irreversible." If scientists can create a drug that targets Aß*, he says, then we may eventually have a treatment to prevent, arrest, or reverse memory impairment associated with Alzheimer's disease.