Noninvasive brain wave treatment reduces Alzheimer's pathology, improves memory in mice

Recent NIA-supported research offers evidence in mice that stimulation of gamma brain waves reduces Alzheimer’s-related proteins and slows neurodegeneration associated with the disease.

Healthy brains feature rhythmic patterns, or brain waves, that operate at different frequencies. Gamma brain waves, which oscillate at roughly 30 to 100 Hz, are associated with higher-order cognitive functions and are known to decrease in the brains of people with Alzheimer’s.

Previously, researchers at the Massachusetts Institute of Technology (MIT) discovered that exposing Alzheimer’s mouse models to LED lights flickering at 40 Hz could stimulate gamma waves, which not only reduced levels of beta-amyloid and tau—proteins associated with Alzheimer’s—but also boosted the activity of microglia in clearing harmful debris.

In a study reported in Cell April 4, MIT researchers further explored the effects of gamma wave stimulation using sound in Alzheimer’s mouse models. Clicks played at 40 Hz an hour a day for a week reduced levels of beta-amyloid in the auditory cortex and nearby hippocampus, a part of the brain responsible for learning and memory. Stimulated mice performed better on memory tasks, including recognizing objects and navigating a water maze to find a hidden platform. Researchers also saw changes in activation responses in microglia and astrocytes, cells involved in clearing debris, and in blood vessels.

Researchers then exposed mice to a combination of light and sound stimulation, which expanded the effects beyond the visual and auditory cortex to the prefrontal cortex, an area of the brain important for planning and completing tasks. Using imaging analysis, the scientists found a unique clustering effect of microglia around amyloid deposits in stimulated mice and reduced amyloid pathology. The effects were short-lived, however, diminishing a week after stimulation.

In a study published May 2 in Neuron, MIT researchers tested the effects of longer-term treatment by exposing mouse models with more advanced Alzheimer’s disease to up to 6 weeks of gamma entrainment by visual stimulation. Results showed stimulation increased gamma brain waves in the visual cortex and higher-order brain areas, including the hippocampus and prefrontal cortex. Continuing stimulation also preserved neuronal and synaptic density in these brain regions, improved performance on memory tasks, and reduced inflammation. Findings point to an overall neuroprotective effect, even in the later stages of neurodegeneration, the researchers reported.

Results of this research add to previous investigations of gamma wave stimulation as a possible treatment for Alzheimer’s disease. Researchers are planning studies to determine if the benefits could translate to humans.

These studies were funded by NIA grants RF1AG047661 and RF1AG054321.

References:

Martorell AJ, et al. Multi-sensory gamma stimulation ameliorates alzheimer’s-associated pathology and improves cognition. Cell. 2019 April;177(2):256-271.e22. doi: 10.1016/j.cell.2019.02.014. Epub March 14, 2019.

Adaikkan C, et al. Gamma entrainment binds higher-order brain regions and offers neuroprotection. Neuron. 2019 June;102(5):929-943.e8. doi: 10.1016/j.neuron.2019.04.011. Epub May 7, 2019.