WASHINGTON — Tests on mice suggest the brain damage caused by Alzheimer’s disease may be at least partly reversible, researchers reported Thursday.
Their genetically altered mice regained the ability to navigate mazes after the genes that caused their dementia were de-activated.
This suggests that the brain damage caused by Alzheimer’s is not permanent, they wrote in their report, published in the journal Science.
"I was astonished. I didn’t believe the results when I saw them," said Alzheimer’s researcher Karen Ashe of the University of Minnesota, who led the study.
"When I saw the memory getting better I actually thought I had done something wrong in the experiment."
Alzheimer’s is a brain-destroying disease that affects an estimated 4.5 million people in the United States alone and millions more globally. As the population gets steadily older, experts estimate this number will balloon to as many as 16 million by 2015 in the United States.
Outward symptoms start with memory loss, which progresses to complete helplessness as brain cells are destroyed. In the brain, neurons die as messy plaques and tangles of protein form.
The two proteins involved are unhealthy forms of natural brain compounds called amyloid beta and tau protein.
Ashe’s team worked with mice genetically engineered to develop the mutant tau, but this mutation could be stopped — or de-activated — with use of a drug called doxycycline.
As expected, the mice developed dementia and had brain atrophy similar to human Alzheimer’s disease.
And when the engineered gene was turned off, memory loss stopped, as expected. But the mice did not merely stop getting worse. They got better.
"Even mice that had lost half the neurons that are involved in forming memories, when we removed the molecule causing the memory loss from the remaining neurons by turning off the genes, the mice were able to learn and remember new information," Ashe said in a telephone interview.
"No one suspected so many neurons would still be able to function."
FROM MICE TO MEN
She noted that it is a long way from treating a mouse to treating a person.
"How are we ever going to turn off the gene in humans?" Ashe asked. What might be possible, she said, would be stopping the production of the mutant proteins. And current vaccine efforts are aimed at removing the bad proteins from the brain.
"The point that makes us hopeful is the remaining neurons were functioning," she said. "When we removed the molecules that presumably were causing the malfunction, the mice were able to perform better."
Ashe said her team used a swimming maze test, in which mice must swim and find an underwater platform to stand on.
"The maze situation is very similar to parking a car in the parking lot and remembering where you parked it," she said.
William Thies, vice president for medical affairs at the Alzheimer’s Association, said at the very least the mouse would be a useful tool for testing new therapies.
"It at least opens the possibility that people will get better," Thies said in a telephone interview.
The other interesting finding, Ashe said, was that the tangles of brain cells were not in themselves, evidently, toxic to surrounding brain tissue.
"The neurofibrillary tangles, which are one of two major pathological hallmarks of Alzheimers disease, turn out not to be involved in causing memory problems, at least in mice," she said.
Some process may be going on at a microscopic level, and the tangles may be a result but not a cause of the brain damage, she said.
