Memories 'taken' by Alzheimer's could possibly be retrieved

"Memories wiped by Alzheimer's could be revived, research suggests," The Daily Telegraph reports.

Research involving mice suggests memories are not destroyed by Alzheimer's disease – rather, there are difficulties recalling them.

Researchers tested the memory of mice using a technique called contextual fear conditioning. This involves applying electric shocks to their feet inside a cage with a specific scent, colour, and shape.

Mice with a working memory will freeze when introduced to the cage later on in an attempt to play dead in the presence of what they perceive to be a predator.

The US researchers used mice bred to have a disease similar to Alzheimer's. They wanted to see whether they could bring back forgotten memories by using lights to directly stimulate the nerve cells associated with memory.

The "stimulated" mice exhibited a freeze response, while an untreated control group did not. The researchers say this shows that the problem is with the retrieval of memories, not that the memories have been destroyed or corrupted, in the same way as a damaged file on a computer might be.

However, the researchers cautioned that the technique they used is not suitable for humans, and human Alzheimer's disease may work in a different way.

The study was met with cautious acclaim by experts in the field, who applauded the "elegant" study, but reiterated that the results are not "directly translatable" to people. Still, at some point in the future it may be possible to pull back memories "stolen" by Alzheimer's. 

The study was carried out by researchers from Massachusetts Institute of Technology (MIT), and was funded by RIKEN Brain Science Institute, the Howard Hughes Medical Institute, and the JPB Foundation.

It was published in the peer-reviewed journal, Nature.

The Guardian and The Daily Telegraph published remarkably similar stories outlining the experiment. They went on to quote the same experts, who warned that the techniques used in the study could not be used in humans.

The Mail Online focused on the study's images of brain cells, which they said showed "what a memory looks like". Their story was broadly accurate, but did not mention differences between Alzheimer's disease in humans and the form it takes in genetically engineered mice. 

This research involved a series of behavioural experiments in laboratory mice, some of which had been bred with genetic modifications that gave them signs and symptoms similar to Alzheimer's disease in humans.

The researchers used the animal experiments to investigate the way Alzheimer's disease affects memory. But the results of animal studies like these, while useful, cannot be directly applied to humans.  

Researchers took mice bred to develop an Alzheimer's-like disease (AD mice) at an age when they had difficulties with long-term (24-hour) memory, but could still demonstrate short-term memory (one hour).

The researchers induced fear responses by applying electric shocks to their feet inside a cage with a specific scent, colour, and shape. They checked that the mice no longer showed a fear response – freezing – in the same cage 24 hours later.

They then used blue light to directly stimulate specific nerve cells in the brain associated with that memory (engram cells). They looked at whether mice recovered their memory of the fear response at the time, or again afterwards.

The researchers used a technique to label the nerve cells involved in memory response with a light-sensitive protein. This allowed them to precisely target the same cells with blue light to see what effect it had on memory.

In a linked set of experiments, researchers looked at what happened to specific nerve cells targeted by repeated light stimulation. They theorised that they would grow additional "spines", which enable the nerves to make new connections with other nerve cells in the brain.

As well as the AD mice, the researchers tested control mice that did not have the Alzheimer's-like disease, and two other types of AD mice bred in different ways. They then looked at whether other types of memory – not just fear response – were affected by light stimulation.  

The researchers found AD mice showed a fear response in the cage where they previously had electric shocks when they were being stimulated by blue light.

But the memories did not last – when they were tested without blue light stimulation a day later, they showed no fear response. The same thing happened when using two other models of Alzheimer's disease mice.

Brain dissection showed repeated blue light stimulation over a period of time could induce certain nerve cells to grow additional "spines" in AD mice. Mice that received treatment to stimulate additional spines were then able to retrieve memories for up to six days.

The researchers also found this spine regeneration technique reversed long-term memory loss in tests of avoiding areas associated with shocks, and finding and exploring new objects placed in cages. 

The researchers said: "To our knowledge, this is the first rigorous demonstration that memory failure in early AD models reflects an impairment in the retrieval of information." In other words, in these animal models the problem is not forming the memory, but retrieving it after a period of time.

However, they warned that, "The underlying mechanism of memory failure in early AD patients may not necessarily parallel the molecular and circuit impairments observed in mouse models of early AD."

They pointed out that in the mouse model of early AD, memory loss happens before the development of amyloid plaques in the brain – characteristic hallmarks of the disease in humans – and some people have amyloid plaques before showing any signs of memory loss.

This is a small but intriguing study, not least because of the apparent ability of scientists to pinpoint and label the exact nerve cells involved in the formation of specific memories.

The researchers found their technique of brain stimulation using blue light seemed to have dramatic effects on the memory of mice.

This suggests the AD mice were able to form memories – and, with the right stimulus, they could also retrieve them. This insight helps researchers build a better understanding of how Alzheimer's disease works and how it affects memory.

However, this work may not translate into treatments for people with Alzheimer's disease. As the researchers point out, we already know of some significant differences in the way memory loss and brain degeneration affect mice and humans.

The technique used to directly stimulate the nerve cells involved putting implants in the brain, as well as various other procedures that would not be possible in humans. A treatment similar to deep brain stimulation, which is sometimes used in humans, did not work when tried in the AD mice.

There are also other issues to be aware of. One is that this study only looked at what happened to mice in the early stages of Alzheimer's-like disease. At this point, the mice did not have amyloid plaques in their brains. We don't know whether the treatment would have any effect on later-stage AD mice.

Also, the researchers don't know what happens to memory formation in later Alzheimer's disease. It's possible the ability to form memories and retrieve them also declines. Any treatment that helps people with memory loss in the early stages might be useless as the disease progressed.

Overall, this is an interesting scientific advance, but currently has no application in the treatment of Alzheimer's disease in humans.  

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