Though many have thought it an eventually likelihood that the progression of Alzheimer’s disease could be halted or slowed, none have anticipated the implications of study done on mice where dementia was actually reversed.
This provocatively suggests that Alzheimer’s patients in the future may not suffer the permanent loss of cognition and memory that 4.5 million American patients and their families cope with today. The heart-rending disease may actually be reversible.
“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.”
Ashe and her team created an abnormal form of tau protein, the key suspect molecule that causes the loss of neurons. The mice in the experiment had experienced a severe loss of neurons. While dead neurons could not be revived once tau was removed, “sick” neurons healed themselves and got better.
“That implies that the remaining neurons were functioning improperly,” Ashe said. “If we discover a way to remove the molecules affecting the remaining neurons, Alzheimer’s patients who have lost neurons would regain their ability to learn.”
Scientists trained mice to swim to a platform in a pool of water. Once the mutated gene, based on the tau protein, was introduced, the mice lost their ability to find their way back to the platform. When researchers “turned off” the gene, the mice regained their memory.
“Many of us have thought that the brains of Alzheimer’s patients have live neurons, dead ones and sick ones,” said William Thies, vice president for medical and scientific affairs at the Alzheimer’s Association. “If you remove whatever is irritating the sick ones, they can get better.”
The extent of recovery was also promising as even when half of memory-forming neurons had been lost, the ability to learn and remember new information was restored after turning off the genes, according to Ashe.
The mice were genetically engineered to develop a mutant form of tau. The mutation caused the mice to develop dementia and brain atrophy. It was deactivated with a drug called doxycycline.
Turning off the gene was not able to reverse the number of neurofibrillary tangles in the brain, the other main feature of the disease. The tangles, caused by deposits of a protein called beta-amyloid, are not the cause of memory loss.
Scientists say the ultimate goal in Alzheimer’s treatment is to find therapy that attacks the accumulation of both tau and beta-amyloid.
The form of tau in the mice is not the same as it is in humans. It is hopeful researchers will be able to identify the human form, but the process proves difficult.
“Maybe there are other abnormal forms of tau that have not been found,”said Ashe. “After all, these are not even visible under the microscope.”
The task now remains of finding which form of beta-amyloid and tau to target.
Alzheimer’s is expected to affect as many as 16 million people in the US by 2015.
