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How sensory gamma rhythm stimulation clears amyloid in Alzheimer’s mice

By David Orenstein | The Picower Institute for Learning and Memory

Studies at MIT and elsewhere are producing mounting evidence that light flickering and sound clicking at the gamma brain rhythm frequency of 40 hertz (Hz) can reduce Alzheimer’s disease (AD) progression and treat symptoms in human volunteers as well as lab mice. In a new open-access study in Nature using a mouse model of the disease, MIT researchers reveal a key mechanism that may contribute to these beneficial effects: clearance of amyloid proteins, a hallmark of AD pathology, via the brain’s glymphatic system, a recently discovered “plumbing” network parallel to the brain’s blood vessels.

“Ever since we published our first results in 2016, people have asked me how does it work? Why 40Hz? Why not some other frequency?” says study senior author Li-Huei Tsai, Picower Professor of Neuroscience and director of The Picower Institute for Learning and Memory of MIT and MIT’s Aging Brain Initiative. “These are indeed very important questions we have worked very hard in the lab to address.”

The new paper describes a series of experiments, led by Mitch Murdock PhD '23 when he was a brain and cognitive sciences doctoral student at MIT, showing that when sensory gamma stimulation increases 40Hz power and synchrony in the brains of mice, that prompts a particular type of neuron to release peptides. The study results further suggest that those short protein signals then drive specific processes that promote increased amyloid clearance via the glymphatic system.

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