Sleep sounds for mice could boost Alzheimer’s research


It’s “not practical to put little Beats by Dre [headphones] on mice, although it would be incredibly cute,” Michael Larson says — but the specialized tones they’ll hear while they sleep through an upcoming study could potentially lead to a breakthrough in Alzheimer’s research.

Larson and the apparatus he’s developed for the study, based on the mechanism behind his Sleep Shepherd sleep aid, are poised at the promising intersection of discoveries about deep sleep, brain activity, beta-amyloid plaques and Alzheimer’s disease.

The hope is that this study, about to be launched by the Knight Alzheimer’s Disease Research Center team at Washington University School of Medicine in St. Louis, will show whether playing special tones to sleeping mice can reduce the levels of Alzheimer’s-linked beta-amyloids in their brains.

“Work from Dr. John Cirrito and Dr. David Holtzman’s labs here at Washington University has shown that amyloid beta, the protein that builds up in the brain of individuals with Alzheimer’s disease, fluctuates during sleep and wake,” Dr. Carla Yuede, assistant professor in the Department of Neurology at Washington University School of Medicine, said in an email. “In mice, levels of the protein are higher during active periods and lower during sleep, and sleep disruption leads to a more rapid build up of amyloid beta in the brain.

“We hope to determine if Dr. Larson’s method using binaural tones to improve sleep quality changes the levels of amyloid beta in the brains of our mouse model of Alzheimer’s disease. And, if it does, how rapidly does this occur, and does it lead to improvement in memory function in these mice.”

Larson is founder and president of Springs-based Mind Rocket Inc., El Pomar Chair of Engineering and Innovation at UCCS, inventor of the Sleep Shepherd (the sleep hat) and president of Sleep Shepherd (the company). He’s had a passion for understanding and improving sleep since his daughter was diagnosed with a sleep disorder in high school and suffered side effects from sleep medication.

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As he delved into the area, Larson discovered that those with recognized disorders were not the only ones suffering.

“The CDC has identified that we’ve got 70 million Americans who are not getting sufficient sleep and their lives suffer the consequence,” he said. “So I begin to take it to heart — how can we get somebody’s brain to slow down naturally, instead of people taking drugs? Because most drugs like Ambien, Lunesta, and all of the benzodiazepines, don’t really put people in a sleepy state — they anesthetize people, and their brain activity doesn’t look like real sleep.”

Larson experimented with brain entrainment methods to develop the Sleep Shepherd, and eventually settled on using auditory signals called binaural tones to help people’s brains slow down naturally.

“We moderate that with a single channel EEG brainwave sensor, so we’re monitoring what people’s brain waves are doing in order to customize those tones,” he said. “Here, the translation for the mice is that we’re looking at using the same binaural tones, adjusted to be appropriate for mice, because mice hear in a different frequency range than do people. We know what brain wave rate in mice corresponds to sleep, so we’re going to have our effect at a sleepy frequency for mice. So that’s the connection with the Sleep Shepherd: Just like the Sleep Shepherd slows people’s brains down, we’re going to use the same principle to slow the mice brains down and then hopefully see this positive effect on beta-amyloid reduction.”

There’s an urgent need to tackle Alzheimer’s disease, Larson said.

“One in nine Americans over the age of 65 has some stage of Alzheimer’s disease,” he said. “We’ve got the Baby Boomer generation now coming into that age where Alzheimer’s is going to be a big problem for a lot of people, and as a society we want to be able to care for these people — but how we are going to do that is unclear.

“Alzheimer’s is the biggest single cause of dementia,” he added. “And here’s another alarming statistic that gives us pause: Of the top 10 killers in America, Alzheimer’s — which comes in at No. 6 — is the only one on the list that we cannot treat, or even slow down. We have no known way of doing that.”

Alzheimer’s is a degradation of the neuron pathways in the brain, Larson said, and its hallmark is a buildup of tangled proteins called beta-amyloids.

“It used to be that we thought these plaques suddenly attacked people’s brains, typically some time after the age of 65,” he said, “but now we know that actually those plaques build up over decades… .”

Why could sleep be the solution?

“When you’re in deep sleep (and by deep sleep we mean low brain wave activity rate, when you’re zonked out) … during that time your brain shrinks slightly,” Larson said, “and the contraction causes pathways to open up in the brain itself, primarily around blood vessels, that permit a perfusion of cerebrospinal fluid to literally wash through your brain and — you guessed it — clear out some of these beta-amyloid plaques.”

Larson connected with the Knight Alzheimer’s Disease Research Center team, which had developed a new technique capable of tracking changes in beta-amyloid content in a mouse’s cerebrospinal fluid in real time.

“So I visited with them and I showed them what I’m doing … They got stoked and said, ‘We want to test mice exposed to your binaural tones, to see if we can replicate that study for decreasing the beta-amyloid load,’ and the implications here are huge,” he said. “And so I have now constructed an apparatus that allows us to, in a humane way, expose mice to the specialized tones that have to be played in stereo.”

Testing should start in about two weeks, he said.

If it works, what then?

“If … we do discover that we can intentionally activate brain cleaning and that it has that positive effect of reducing the evidence of Alzheimer’s … then I have already shown with my product, that people can sleep listening to those very tones, because there are 20,000 people out there who are sleeping with [the Sleep Shepherd],” Larson said. “So we know that we could make this available to literally everybody, and it can help with brain maintenance in regular life, which would be fantastic. And what we’re talking about is a non-drug solution. It’s very exciting.

“Again, I do have to be careful not to oversell at this point, but that is what I’m excited about — and as long as there’s a potential I want to pursue it wholeheartedly.”