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<\/div>A cross-section of a mouse\u2019s brain highlighting neurons that seem to release a molecule that increases toxin clearance<\/p>\n
Tsai Laboratory\/MIT Picower Institute<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/p>\n
A new explanation has emerged for why an experimental treatment for Alzheimer\u2019s disease involving sounds and flickering lights may help slow cognitive decline. The frequencies involved seem to ramp up the brain\u2019s waste disposal networks, which boosts the clearance of beta-amyloid <\/a>and other toxic proteins that contribute to memory and concentration problems.<\/p>\n \u201cOnce we understand the mechanism, we can probably figure out how to further optimise this whole concept and improve the efficacy,\u201d says Li-Huei Tsai<\/a> at the Massachusetts Institute of Technology.<\/p>\n The treatment involves exposing people to lights flickering at a frequency of 40 times a second, or 40 hertz, and a low-pitched sound, also at 40 Hz. Typically, the stimulation is given for an hour a day.<\/p>\n Key to the novel approach is that large networks of brain cells naturally fire in sync with each other at different frequencies \u2013 known as brainwaves. Brainwaves of around 40 Hz are often seen when people are concentrating and when they are forming or accessing memories.<\/p>\n As it was known that visual or auditory stimulation at a certain frequency can boost brainwaves at that same frequency, in 2016, Tsai\u2019s team decided to investigate if 40 Hz stimulation might boost cognitive abilities in people with Alzheimer\u2019s.<\/p>\n <\/p>\n Their group and others showed that this lowered amyloid build-up in mice with a version of Alzheimer\u2019s and had cognitive benefits in small trials in people with the condition<\/a>, with a larger trial ongoing. But it was unclear how the treatment might work, with another idea being that it boosts the function of the brain\u2019s immune cells.<\/p>\n Now, it seems the special lights and sound work by enhancing the function of the brain\u2019s drainage system, also known as the glymphatic system<\/a>.<\/p>\n In the latest work, Tsai\u2019s team carried out a series of experiments to study the treatment\u2019s mechanism in mice that had been genetically altered so that they usually develop a build-up of amyloid as they get older and have worse memories than typical mice.<\/p>\n As expected, when the animals were exposed to the light and sounds, they had less amyloid. The new finding was that during the treatment, they had a greater amount of cerebrospinal fluid entering the brain and more waste fluid leaving it through the glymphatic vessels.<\/p>\n This seemed to be happening because nearby blood vessels were pulsating more, which could help push the glymphatic fluid through its vessels, and because of more water flowing into the glymphatic system.<\/p>\n The team also found that the activity of a specific type of brain cell, known as an interneuron, seemed to be triggering the increased glymphatic flow by releasing a molecule called vasoactive intestinal peptide. When the team chemically blocked this molecule\u2019s production, the treatment no longer boosted amyloid clearance.<\/p>\n