Changes in brain waves called gamma oscillations have been seen in several brain disorders, including in patients with Alzheimer's disease. Now, a study of mice suggests a type of light therapy - where flickering light shines into the eyes and induces gamma oscillations in the brain - may offer a noninvasive treatment for Alzheimer's disease.
The researchers - from the Massachusetts Institute of Technology (MIT) in Cambridge - report their findings in the journal Nature.
One of the hallmarks of Alzheimer's disease is the formation of faulty protein deposits called beta-amyloid plaques that are thought to be toxic to brain cells and interfere with normal brain function.
Previous research has also suggested people with Alzheimer's disease have impaired gamma oscillations. These brain waves - in the 25-80 hertz or cycles per second range - are thought to be necessary for normal functioning of processes such as memory, perception, and attention.
In the new study, the MIT researchers found mice genetically engineered to develop Alzheimer's disease showed reduced gamma oscillations in the brain before the formation of beta-amyloid plaques and a decline of learning and memory skills essential for solving a maze.
Senior author Li-Huei Tsai, a professor of neuroscience, and colleagues go on to show that inducing gamma oscillations with a light-flickering regimen reduces brain levels of beta-amyloid in pre-plaque, younger mice and leads to fewer plaque deposits in older mice.
Prof. Tsai says more research needs to be done before we can say if the therapy works for human patients with Alzheimer's disease. She explains:
"It's a big 'if',' because so many things have been shown to work in mice, only to fail in humans. But if humans behave similarly to mice in response to this treatment, I would say the potential is just enormous, because it's so noninvasive, and it's so accessible."
Gamma oscillations reduced beta amyloid in hippocampus
Alzheimer's disease is a progressive, irreversible brain disorder that destroys thinking and memory and robs people of their ability to have an independent life and take care of themselves.
- An estimated 5.4 million Americans are living with Alzheimer's disease
- It is the only disease in the top 10 causes of death in the United States that cannot be prevented, cured, or slowed
- Nearly 1 in 5 Medicare dollars are spent on Alzheimer's and other dementias.
Estimates suggest 47 million people worldwide are living with dementia, of which Alzheimer's is the most common cause. This number is set to reach 132 million in 2050.
While the exact causes of Alzheimer's are unknown, scientists know people affected by the disease undergo complex, toxic brain changes - such as formation of beta-amyloid plaques - that can start a decade or more before problems with memory and thinking appear.
For the study, the researchers induced gamma oscillations at 40 hertz in the hippocampus - a brain region important for forming and retrieving memories. They used an approach called optogenetics to stimulate a group of cells called interneurons, which synchronize the gamma activity of brain cells that communicate with each other.
After an hour of stimulation at 40 hertz, the researchers found hippocampal levels of beta-amyloid proteins fell by 40-50 percent. This did not happen at other frequencies they tried.
The researchers then built a device comprising a strip of LEDs that can be programmed to flicker at different frequencies and can induce gamma oscillations in the brain when shone in the eyes.
They found that 1 hour of exposure to light flickering at 40 hertz set up gamma oscillations and halved beta-amyloid levels in the visual cortex of mice in the early stages of Alzheimer's disease. However, the beta-amyloid proteins went back up to their previous levels within 24 hours.
Gamma oscillations boost clearance by microglia cells
In further tests with longer exposure on mice in more advanced stages of Alzheimer's disease, the researchers found markedly reduced beta-amyloid levels and plaque deposits.
They are currently investigating how long these effects last and whether they can also drive gamma oscillations beyond the visual cortex.
The researchers also found that gamma oscillations reduce another hallmark of Alzheimer's disease - abnormal tau proteins that form tangles in the brain.
Finally, the team also showed that gamma oscillations improve the brain's ability to clear out faulty proteins. This job is normally performed by immune cells called microglia, says Prof. Tsai. "They take up toxic materials and cell debris, clean up the environment, and keep neurons healthy."
In patients with Alzheimer's disease, microglia cells become inflammatory and secrete chemicals that are toxic to brain cells. But, when they increased gamma oscillations in the mice, the researchers found their microglia cells changed shaped and were active in clearing away beta-amyloid proteins.
Prof. Tsai says it looks like boosting gamma oscillations acts in two ways: it reduces the production of beta-amyloid, and it also increases their clearance by microglia cells.
"This important announcement may herald a breakthrough in the understanding and treatment of Alzheimer's disease, a terrible affliction affecting millions of people and their families around the world."
Michael Sipser, dean of MIT's School of Science
The following video from MIT sums up the research and its implications: