Cross-section of mouse brain highlights neurons that appear to release a molecule that increases toxin removal
Tsai Lab/MIT Picower Institute
A new explanation has emerged for why an experimental Alzheimer’s disease treatment involving sound and flashing lights may help slow cognitive decline. The frequencies involved appear to enhance the brain’s waste-disposal networks, thereby promoting the removal of beta-amyloid and other toxic proteins that cause memory and attention problems.
“Once we understand the mechanism, we can figure out how to further optimize the whole concept and increase efficacy,” said Cai Lihui at MIT.
The treatment involves exposing people to lights that flash at a frequency of 40 times per second, or 40 Hz, and low-pitched sounds, also at 40 Hz. Typically, stimulation is given for one hour each day.
The key to this new approach is that large networks of brain cells naturally fire in sync with each other at different frequencies, called brain waves. Brain waves around 40 Hz are often seen when people are concentrating and forming or accessing memories.
It is known that visual or auditory stimulation at a specific frequency can enhance brain waves at that frequency, and in 2016, Tsai’s team decided to study whether 40 Hz stimulation could enhance cognitive abilities in Alzheimer’s patients.
Their team and others have shown that this reduces amyloid accumulation in mice with a form of Alzheimer’s disease and has cognitive benefits. Small trials on people with the disease, larger trials are underway. But it’s unclear how the treatment works, with another idea being that it could boost the function of the brain’s immune cells.
Now, special lights and sounds appear to work by enhancing the function of the brain’s drainage system, also known as the glymphoid system.
In the latest study, Cai’s team conducted a series of experiments to study the mechanisms of the treatment in genetically modified mice that typically develop amyloid as they age and have better memory than normal mice. worse.
As expected, when the animals were exposed to light and sound, their amyloid decreased. The new finding is that during treatment, they had more cerebrospinal fluid entering the brain and more waste fluid leaving the brain through lymphoid vessels.
This appears to happen because nearby blood vessels pulse more, which helps push lymphatic fluid through their vessels, and more water flows into the lymphatic system.
The team also found that the activity of a specific type of brain cell called interneurons appears to trigger an increase in the flow of lymphoid fluid by releasing a molecule called vasoactive intestinal peptide. When the team chemically blocked the production of this molecule, the treatment no longer promoted amyloid clearance.
McCann Nedergaard A professor at the University of Rochester in New York who helped discover the lymphoid system says the finding fits with what we already know. “The brain, blood, and cerebrospinal fluid are all contained within the skull. If blood volume increases, the volume of cerebrospinal fluid must move because brain tissue is not compressible.”
In an accompanying article natural medicineNedergaard said a better understanding of the mechanisms by which toxins are cleared from the brain “could be the key to unlocking (its) therapeutic potential.”
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