Memories banished by Alzheimer’s can in theory be rescued by stimulating nerve cells to grow new connections, a study has shown.



The research, conducted in mice, raises the possibility of future treatments that reverse memory loss in early stages of the disease. Scientists used a technique called optogenetics, which uses light to activate cells tagged with a special photo-sensitive protein.

It was tested on mice with Alzheimer’s-like symptoms that quickly forgot the experience of receiving a mild electric shock to their feet. After tagged cells in their brains were stimulated with light, their memory returned and they displayed a fear response when placed in the chamber where the shock had been applied an hour earlier.

The optogenetic treatment helped the neurons re-grow small buds called dendritic spines, which form synaptic connections with other cells. Although the same technique cannot be used in humans, the research points the way to future memory-retrieving therapies, say the researchers.

Lead scientist Prof Susumu Tonegawa, from the Picower institute for learning and memory at the Massachusetts Institute of Technology (MIT) in the US, said: “The important point is, this a proof of concept. 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, published in the journal Nature, specifically targeted memory cells in the hippocampus region of the brain previously identified by Tonegawa’s team.

Two different strains of mice, genetically engineered to develop Alzheimer’s symptoms, plus a control group of healthy animals, were used in the experiment.

Longer-term activation of forgotten memories was induced by stimulating new connections between the hippocampus and entorhinal cortex brain regions.

Tonegawa said: “It is possible that in the future some technology will be developed to activate or inactivate cells deep inside the brain, like the hippocampus or entorhinal cortex, with more precision. Basic research as conducted in this study provides information on cell populations to be targeted, which is critical for future treatments and technologies.”

British expert Prof Richard Morris, a neuroscientist at the University of Edinburgh, said: “When someone with early Alzheimer’s is forgetful, it is tempting to suppose that the memory is lost.

“However, echoing classic work by Elizabeth Warrington at the National h in Queen Square, London over 30 years ago, forgetfulness can also happen when the recall or retrieval mechanisms of the brain are compromised.

“This fine study using a genetic mouse model of Alzheimer’s disease coupled to optogenetics offers the tantalising idea that ‘tagged’ memories can be reactivated by light. The fascinating technique developed by the Nobel laureate Susumu Tonegawa and his team at MIT cannot be used in humans, but it indicates that forgetfulness in [mice with Alzheimer’s symptoms] may also be an access problem.”

Dr Doug Brown, director of research at Alzheimer’s Society said: “One of the key issues with understanding memory loss in Alzheimer’s is that we don’t know whether people are having problems storing memories or recalling them. This study in mice helps us to unpick the underlying processes and problems that lead to memory loss in the earliest stages of Alzheimer’s disease – this new evidence suggests that memory recall is the issue.

“While interesting, 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.”



Dr Simon Ridley, science director at Alzheimer’s Research UK, said: “While the findings raise intriguing questions about whether it’s possible to recover lost memories, there is a long way to go to understand this process in people and how it’s affected over the course of a disease like Alzheimer’s.

“The mice in this study had not started to develop some of the other key features of Alzheimer’s, such as the build-up of toxic proteins, and these changes are also likely to impact on normal nerve cell function.”