Memory loss is one of the hallmarks of Alzheimer's and heartbreaking for loved ones to watch progress. Gone are the details of a first love or a child's wobbly first steps. The achievements of a distinguished 30-year career. And the tall tales of traveling the globe that once had everyone rolling on the floor with laughter.
Scientists had assumed for a long time that the disease destroys how those memories are encoded and makes them disappear forever. But what if they weren't actually gone — just inaccessible?
A new paper published Wednesday by the Massachusetts Institute of Technology's Nobel Prize-winning Susumu Tonegawa provides the first strong evidence of this possibility and raises the hope of future treatments that could reverse some of the ravages of the disease on memory.
“The important point is, this is a proof of concept," Tonegawa said. "That is, even if a memory seems to be gone, it is still there. It’s a matter of how to retrieve it."
The research, described in the journal Nature, involved two groups of mice. One was a normal control and the other was genetically engineered to have Alzheimer's-like symptoms. Both groups were given a mild electric shock to their feet. The first group appeared to remember the trauma of the incident by showing fear when placed back in the box where they had been given the shock. The Alzheimer's mice, on the other hand, seemed to quickly forget what happened and did not have an upset reaction to the box.
Their reaction changed dramatically when the scientists stimulated tagged cells in their brains in the hippocampus — the part of the brain that encodes short-term memories — with a special blue light. When they were put back in the box following the procedure, their memories of the shock appeared to have returned, and they displayed the same fear as their healthy counterparts.
Tonegawa and his colleagues wrote that the treatment appears to have boosted neurons to regrow small buds called dendritic spines that form connections with other cells.
The revelations have “shattered a 20-year paradigm of how we’re thinking about the disease,” Rudy Tanzi, a Harvard neurology professor who is not involved in the research, told the Boston Herald. He said that since the 1980s, researchers believed the memories just weren't getting stored properly.
The technique used in the study — optical stimulation of brain cells, or "optogenetics" — involves the insertion of a gene into parts of a brain to make them sensitive to blue light and then stimulating them with the light.
In a commentary accompanying the paper, Prerana Shrestha and Eric Klann of the Center for Neural Science at New York University said that the research employed a "clever strategy" and that "the potential to rescue long-term memory in dementia is exciting."
Doug Brown, director of research at the Alzheimer’s Society, cautioned that the technique is not something that can be translated into a procedure that is safe for the estimated 44 million people worldwide with dementia just yet.
“While interesting," he told the Guardian, "the practicalities of this approach — using a special blue light to stimulate memory — means that we’re still many years away from knowing if it would be possible to restore lost memories in people."
Electrical stimulation of the brain may be one alternative scientists can pursue, according to Christine Denny, a neurobiologist at Columbia University. Nature reported that early trials showed that deep-brain stimulation of the hippocampus may improve memory in some Alzheimer's patients.