So the researchers turned again to their tau transgenic mouse, which features a unique on-off “switch”¬ to control the expression of the mutant gene so that the disease could be studied at both early and late stages.
During these experiments, the Mayo Clinic group and their collaborators were stunned to find that they could reverse tau pathology early on, and restore memory to mice that had started to develop cognitive problems.
But researchers were in for an even bigger surprise, Dr. Hutton says. “What was amazing, absolutely staggering in fact, is that when we aged the mice further -- to the point where the pathology was quite severe, a lot of neurons had died, and the mouse couldn’t remember any of its tasks -- when we hit this molecular switch, the mouse recovered a lot of its memory.”
To the research team, this demonstrated that Alzheimer’s is potentially a reversible process: that if deposition of AB is not stopped in time, then it may be possible to halt tau degradation and restore damaged nerves. “Once you get the disease, the effectiveness of AB therapy may be limited, so we hope tau will be potentially a more exciting target,” Dr. Hutton says. “If we are able to remove the blockage that is clogging microtubules, it may be that the system will just start again, with neurons back functioning normally.”
Dr. Lewis says the studies suggest that toxicity to neurons caused by tau begins before tangles develop. “If so, we may be able to repair that process so that the neuron can rebound,” she says.
Their achievement was reported in 2005 in Science.
“These tau findings changed our ideas about what the potential for recovery is in Alzheimer’s, but also about what is causing memory loss in the patients in the first place,” Dr. Hutton says. “Our mice lost between