Scientists looking for drugs to treat Alzheimer's disease have a new ally: a genetically engineered mouse that suffers memory loss and ruined brain cells just like humans who have the mind-robbing disorder.
In a report published Friday in the journal Science, a team of researchers led by Dr. Karen Hsiao of the University of Minnesota announced it has inserted a mutated human gene into a mouse embryo to create a breed of laboratory rodents that develop the symptoms of Alzheimer's disease.Experts said the work is a major boost to efforts to find new drugs to treat the disease and to understand how Alzheimer's disease destroys memory and, eventually, life itself.
Maze experiments testing the animals' thinking ability show that as the new mouse ages it suffers from a loss of memory that mimics the decline seen in humans, Hsiao said. The mouse brain also develops beta amyloid plaques, a substance found in the brains of Alzheimer's patients.
"This is the first time that anybody has made a mouse that shows an association between plaques and a functional loss of learning memory which is very much like Alzheimer's disease," Hsiao (pronounced sh-HOW) said in an interview.
Dr. Thomas Chase, an Alzheimer's disease expert at the National Institutes of Health, called the findings "good news for patients with Alzheimer's."
"It will enable the testing of drugs that get at the basic disease process," he said.
Drugs now available, he said, appear to treat only Alzheimer's symptoms.
Zaven Khachaturian, a scientist who heads the Alzheimer's Association Ronald and Nancy Reagan Research Institute, said the most important element of the new mouse is that it "shows the behavioral deficits that are comparable to what is happening in humans" with Alzheimer's.
He said mice developed in other labs have Alzheimer's brain lesions like those in humans but exhibit none of the changes in memory and learning ability that Hsiao demonstrates with the Minnesota mouse.
"Caregivers want their loved ones to retain their functional abilities as long as possible," Khachaturian said. "This mouse model should help us find those therapies."
The Minnesota researchers "made" the mouse by putting into a mouse egg the human gene that manufactures amyloid precursor protein. This substance helps form beta amyloid deposits in the brains of Alzheimer's patients.
The resulting mouse was then mated with a normal mouse, Hsiao said, and half the offspring had the Alzheimer's gene.
"We call it the TG2576 mouse," Hsiao said. "We haven't given it a cute name."
Mouse behavior was tested by putting the animals into a 3-foot-square pool of water surrounded by bright colors and patterns. Inside the pool was a platform refuge.
In training sessions, the mice learned to find the platform by lining it up with the bright background patterns. Normal mice memorized this location and quickly found it in later tests. Mice used in the testing were all litter mates, but only about half had the Alzheimer's gene.
When tested at a young age, Hsiao said, the mice with the Alzheimer's gene performed as well as control mice, which have normal genes. But as the animals aged, the Alzheimer's-carrying mice showed a loss of thinking ability.