Forgotten memories have been reawakened in mice with Alzheimer’s disease, suggesting that the condition may not destroy memories but instead impair our ability to recall them.
It has long been assumed that Alzheimer’s disease completely erases memories. The condition involves clumps of proteins known as amyloid plaques and tangles of tau proteins that accumulate in the brain, where they are thought to destroy the neurons that store our memories.
But experiments by Christine Denny at Columbia University and colleagues suggest that memories may not be wiped by Alzheimer’s disease but just become harder to access. What’s more, these memories can be reawakened by artificially activating the neurons they are stored in.
The finding could be revolutionary, says Ralph Martins at Edith Cowan University in Australia. “It has the potential to lead to novel drug development to help with regaining memories,” he says.
To examine how memory is affected by Alzheimer’s disease, the researchers developed a way of visualizing individual memories in mouse brains.
They genetically engineered mice with neurons that glow yellow when activated during memory storage and glow red when activated during memory recall. Two sets of these mice were created — one set that was healthy and one with a condition resembling human Alzheimer’s disease.
Both sets of mice took a memory test. First, they were exposed to a lemon scent and given an electric shock. A week later, they were exposed to the same lemon scent. The healthy mice immediately froze in anticipation of being shocked again. The mice with Alzheimer’s froze almost half as often as the healthy mice, suggesting they did not remember the link between the smell and shock so strongly.
This behavior matched what the team saw in the mice’s hippocampi — the brain regions that record memories.
In healthy mice, the red and yellow neurons overlapped, showing that the mice were retrieving the lemon-shock memory from the same place it had been stored. But in the Alzheimer’s mice, different cells glowed red during recall, suggesting that they were calling up the wrong memories.
This might help explain why people with Alzheimer’s disease commonly experience false memories, Denny says. For example, many people with the condition incorrectly remember where they were during the terrorist attacks of Sept. 11, 2001. The mouse experiments suggest this may be because they are retrieving information from the wrong brain cells.
Using a genetic engineering technique called optogenetics, Denny’s team went on to reactivate the lemon-shock memory in the Alzheimer’s mice. By shining a blue laser down a fiber-optic cable into the brain, they were able to stimulate the memory-storing neurons, prompting the mice to freeze when they smelled the lemon scent.
This shows that “lost” memories may remain in the brain and can be recovered.
Optogenetics is not a technique that can be used in people, because it isn’t yet safe or practical to tinker with our neurons or stick lasers into our brains. But in the future, targeted drugs or techniques such as deep-brain stimulation may help people with Alzheimer’s access their forgotten memories, Denny says.
The next step will be to confirm that the same mechanisms of memory storage and retrieval exist in people with Alzheimer’s disease as in mice, Martins says.
But there are already clues that long-lost memories can be reawakened in people with Alzheimer’s disease, Martins says. “Music is the best example, which has attracted a lot of attention as a way for retrieving memories of the past in these patients, so it makes sense.”
If Denny’s techniques do work in people, they could have wider applications, such as helping witnesses better remember crime scenes or students recall their study notes. We may even be able to tap into forgotten memories from our early childhoods.
However, it’s unlikely we could select specific memories because we wouldn’t know which neurons they were stored in, and some neurons might hold multiple memories, Denny says. “You would not want to bring back bad memories, too.”