Alzheimer’s disease, which affects more than 5 million people in the United States, is characterized by beta-amyloid plaques that are suspected to be harmful to brain cells and to interfere with normal brain function. A unique non-invasive technique using flickering light successfully reduced amyloid plaques and improved memory impairments in a mouse model of Alzheimer’s disease, according to a study published in the journal Cell.
Auditory stimulation combined with light-induced gamma oscillations in the hippocampus and auditory cortex regions of the brain reduces amyloid levels and improves memory in animal models of Alzheimer’s disease. Image credit: Martorell et al, doi: 10.1016/j.cell.2019.02.014.
The brain’s neurons generate electrical signals that synchronize to form brain waves in several different frequency ranges.
Previous studies have suggested that Alzheimer’s patients have impairments of their gamma-frequency oscillations, which range from 25 to 80 Hz and are believed to contribute to brain functions such as attention, perception, and memory.
In 2016, Dr. Li-Huei Tsai of MIT’s Picower Institute for Learning and Memory and co-authors reported the beneficial effects of restoring gamma oscillations in the brains of mice that are genetically predisposed to develop Alzheimer’s symptoms.
In that study, the researchers used light flickering at 40 Hz, delivered for one hour a day. They found that this treatment reduced levels of beta-amyloid plaques and another Alzheimer’s-related pathogenic marker, phosphorylated tau protein. The treatment also stimulated the activity of debris-clearing immune cells known as microglia.
In that study, the improvements generated by flickering light were limited to the visual cortex.
In their new study, the researchers set out to explore whether they could reach other brain regions, such as those needed for learning and memory, using sound stimuli.
They found that exposure to one hour of 40-Hz tones per day, for seven days, dramatically reduced the amount of beta-amyloid in the auditory cortex as well as the hippocampus.
“What we have demonstrated here is that we can use a totally different sensory modality to induce gamma oscillations in the brain. And secondly, this auditory-stimulation-induced gamma can reduce amyloid and tau pathology in not just the sensory cortex but also in the hippocampus,” Dr. Tsai said.
The researchers also tested the effect of auditory stimulation on the mice’s cognitive abilities.
They found that after one week of treatment, the mice performed much better when navigating a maze requiring them to remember key landmarks. They were also better able to recognize objects they had previously encountered.
They also found that auditory treatment induced changes in not only microglia, but also the blood vessels, possibly facilitating the clearance of amyloid.
The scientists then decided to try combining the visual and auditory stimulation, and to their surprise, they found that this dual treatment had an even greater effect than either one alone.
Amyloid plaques were reduced throughout a much greater portion of the brain, including the prefrontal cortex, where higher cognitive functions take place. The microglia response was also much stronger.
“These microglia just pile on top of one another around the plaques. It’s very dramatic,” Dr. Tsai said.
The researchers found that if they treated the mice for one week, then waited another week to perform the tests, many of the positive effects had faded, suggesting that the treatment would need to be given continually to maintain the benefits.
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Anthony J. Martorell et al. Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition. Cell, published online March 14, 2019; doi: 10.1016/j.cell.2019.02.014
