New research in mice reveals that an innovative light and sound stimulation therapy can clear toxic plaque buildup in the brain and reduce some of the symptoms of Alzheimer's disease and impaired cognitive functioning.
The hallmarks of Alzheimer's disease in the brain include the formation of beta-amyloid plaques and the amalgamation of tau, a toxic protein that disrupts the correct functioning of neural networks.
Recent research has suggested that people with this form of cognitive impairment also experience brain wave disruptions.
Neurons (brain cells) produce electrical oscillations of various frequencies, which are called "brain waves."
Research has shown that in Alzheimer's disease, individuals experience a disruption in the activity pattern of gamma waves, the brain waves with the highest frequency.
In recent years, a team of scientists from the Massachusetts Institute of Technology (MIT) in Cambridge has been
Now, the same team, working under the guidance of MIT Prof. Li-Huei Tsai, has found that a combination of light and sound therapy can have a significant effect in improving cognitive functioning in these mouse models.
Encouraged by these findings, which appear in the journal Cell, the researchers are now organizing a clinical trial to test the effects of this novel therapy in humans with this neurodegenerative condition.
Auditory stimulation brings benefits
In their previous study, Prof. Tsai and colleagues employed a light stimulation treatment, which involved exposing mouse models to lights flickering at 40 Hertz for 1 hour per day.
At that point, the researchers found that this noninvasive approach helped reduce levels of both beta-amyloid plaques and phosphorylated tau proteins in the rodents' brains.
Moreover, the team observed that the light stimulation boosted the activity of microglia, a type of neural cell that plays a role in the immune response and works by clearing up cellular debris.
However, this previous research focused only on changes to the brain's visual cortex. In the current study, the scientists decided to go one step further and try to treat other brain regions that are involved in memory and learning processes by using sound stimulation to rebalance gamma brain waves.
Thus, they went ahead and exposed mice to 40 Hertz sounds for 1 hour a day for 7 consecutive days. This auditory stimulation had the effect of reducing beta-amyloid levels not only in the auditory cortex but also in the hippocampus, a brain region that plays a key role in processing and recalling memories.
"What we have demonstrated here is that we can use a totally different sensory modality to induce gamma oscillations in the brain," says Prof. Tsai.
"And secondly," she adds, "this auditory-stimulation-induced gamma can reduce amyloid and Tau pathology in not just the sensory cortex but also in the hippocampus."
More importantly, when the researchers assessed the effect of this sound stimulation treatment on the rodents' cognitive abilities, they found that the mice's memories had improved and that they performed much better on a test that required them to find their way out of a maze by recalling landmarks.
At the end of the treatment, the mice's ability to remember objects that researchers had previously exposed them to had also improved.
Combined approach yields best results
In terms of its physiological impact, the auditory stimulation not only triggered microglial activity but also had an effect on blood vessels and circulation. This, the researchers hypothesize, could help further reduce the levels of toxic proteins in the brain.
Spurred on by these findings, the team then combined light and sound stimulation therapy and were pleasantly surprised to find that this treatment had an even better effect.
The researchers found that the combination approach led to the elimination of beta-amyloid plaques in more brain regions, including the prefrontal cortex, which is essential to higher-order cognitive functioning.
Moreover, it offered a more intense boost to microglial activity. "These microglia just pile on top of one another around the plaques," notes Prof. Tsai, calling the effect "very dramatic."
"When we combine visual and auditory stimulation for a week, we see the engagement of the prefrontal cortex and a very dramatic reduction of amyloid."
Prof. Li-Huei Tsai
The team also found that if they interrupted the treatment after the first week, its positive effects would fade away within just 1 week, which suggests that specialists may have to administer this therapy continuously.
Prof. Tsai and colleagues have already proceeded to ascertain that the new combination therapy is safe in humans, and they are currently enrolling participants with early-stage forms of Alzheimer's in a clinical trial that they have designed to assess the treatment's effect on people.