Strobe lighting has been shown to reduce levels of the toxic proteins seen in Alzheimer’s disease, in findings that raise the tantalising possibility of future non-invasive treatments for the disease.
The study, in mice, found that exposure to flickering light stimulated brain waves, called gamma oscillations, that are known to be disturbed in Alzheimer’s patients. Boosting this synchronous brain activity appeared to act as a cue for the brain’s immune cells, prompting them to absorb the sticky amyloid proteins that are the most visible hallmarks of the disease in the brain’s of people with Alzheimer’s.
The authors caution that a “big if” remains over whether the findings would be replicated in humans – and whether cognitive deficits as well as visible symptoms of the disease would be improved.
“If humans behave similarly to mice in response to this treatment, I would say the potential is just enormous, because it’s so non-invasive, and it’s so accessible,” said Li-Huei Tsai, director of the Picower Institute for Learning and Memory at MIT, and the paper’s senior author.
Alzheimer’s research has faced a number of major setbacks – most recently the failure of Eli Lily’s drug trial – after promising results in rodents did not translate into clinical improvements for patients.
The latest intervention, scientists predict, should be quicker and cheaper to confirm in humans than pharmaceuticals, which typically take more than a decade to develop and assess for safety before the clinical efficacy is even examined.
The study, published on Wednesday in the journal Nature, hinges on the observation that Alzheimer’s patients show a loss of synchronised brain activity, known as gamma oscillations, which is linked to attention and memory.
To restore the activity, the scientists first used mice that had been genetically engineered such that the neurons that generate gamma activity in the brain were sensitive to light. The technique, known as optogenetics, allowed the scientists to artificially cause groups of neurons to fire in unison by pulsing light into the brains of the mice.
After an hour of stimulation, the researchers found a roughly 50% reduction in the levels of beta amyloid proteins in the hippocampus, the brain’s memory centre. Closer inspection showed that the amyloid had been taken up by microglia, the brain’s immune cells.
In a healthy brain, microglia act as chemical rubbish collectors, surveying the local environment, clearing up unwanted compounds, but in Alzheimer’s these cells can lose this function and switch into an inflammatory state in which they secrete toxic compounds instead. Strengthening gamma oscillations appeared to switch the microglia back into a productive state.
Next, the scientist showed that gamma oscillations could also be stimulated non-invasively in the visual brain region simply by exposing the mice to a flickering light. At 40Hz the flicker of the light is barely discernible and would be “not offensive at all” for a person to have in the background.
After being given one hour of flickering light each day for a week, the scientists saw a 60% reduction of harmful amyloid plaques in the brains of the mice.
Ed Mann, an associate professor of neuroscience at the University of Oxford, said: “I was surprised, and it’s exciting, that such a simple stimulus can target a molecular pathway and have such an effect in an hour.”
Questions remain, however, about whether boosting gamma oscillations and sweeping amyloid plaques out of the visual brain region would help with memory, which is centred in the hippocampus, or broader cognitive abilities.
David Reynolds, chief scientific officer at Alzheimer’s Research UK, said: “It is conceivable that changing brain cell rhythms could be a future target for therapies, but researchers will need to explore how light flickering approaches could not only reduce amyloid in the visual area of the brain but in those areas more commonly affected in Alzheimer’s.”
The authors suggest that it may be possible to take a multi-sensory approach, using a combination of flashing lights and vibrating chairs. Tsai and Ed Boyden, a colleague at MIT and co-author, have started a company called Cognito Therapeutics to pursue tests in humans.
There are 850,000 people with dementia in Britain and this figure is expected to reach 1 million by 2025. Earlier this year, dementia overtook heart disease as the leading cause of death in England and Wales.
