But senior author Susumu Tonegawa, of the Department of Brain and Cognitive Sciences at Massachusetts Institute of Technology (MIT), and colleagues suggest that individuals with early Alzheimer’s still have the ability to form new memories – they just have difficulty retrieving them. While optogenetics can not now be used in humans, the findings raise the hope – and possibility – that future treatments might indeed reverse some of the memory loss in early-stage Alzheimer’s patients, the researchers say. Through the use of fibre-optic light stimulation, the team was able to regrow these spines, and the mice’s memories were restored. That led the team to wonder whether this might also be true for the memory loss seen in the early stages of Alzheimer’s disease, which occurs before characteristic amyloid plaques appear in patients’ brains. But the researchers expect that the the technique would only work for a few months in mice, or two to three years in humans, before the disease advances enough to erase any gains.
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The researchers then showed that while the mice can not recall their experiences when prompted by natural cues, those memories are still there.
Last year, Alzheimer’s and other dementias cost the United States around $226 billion.
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. With the memories now firmly embedded, the mice remembered to be afraid of the box, even when the light was off.
Mouse memory is often inferred from learned behavior, in this case associating an unpleasant footshock with a particular cage.
The researchers placed the mice back into the chamber and activated the modified neurons by shining a light on them. This memory boot camp worked because it boosted the number of docking sites on memory-holding nerve cells in the mice with Alzheimer’s-related genes.
The mice immediately showed fear. Previous work had shown that spines grow when neurons undergo long-term potentiation, a persistent strengthening of synaptic connectivity that happens naturally in the brain but can also be artificially induced through stimulation.
The study, reported in Nature, contradicts the notion that Alzheimer’s prevents the brain from making new memories. During their experiments, the researchers were able to illuminate the infected neurons of the mice using optical fibres implanted in their brains. Normal mice learned to fear the box, but the mutant mice did not, because they did not remember being shocked. The study found that despite the same rate of shrinkage observed in men and women, the verbal memory of women still performed better.
“This is a remarkable study providing the first proof that the earliest memory deficit in Alzheimer’s involves retrieval of consolidated information”, said Rudolph Tanzi, a professor of neurology at Harvard Medical School, who was not involved in the research.
The American Academy of Neurology, an association of 30,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care.
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While further research is underway, say the authors, there are important changes that could be made to today’s diagnostic tools. “Basic research as conducted in this study provides information on cell populations to be targeted, which is critical for future treatments and technologies”.
