Brain waves show promise against Alzheimer’s protein in mice

Flickering light induces nerve cells to trigger immune response to amyloid-beta

amyloid-beta comparison

RIDE THE WAVES Compared with a mouse that received random brain stimulation (right), a mouse stimulated to produce more gamma waves (left) had less amyloid-beta (green) in its hippocampus.

H.F. Iaccarino et al/Nature 2016

Flickering light kicks off brain waves that clean a protein related to Alzheimer’s disease out of mice’s brains, a new study shows. The results, described online December 7 in Nature, suggest a fundamentally new approach to counteracting Alzheimer’s.

Many potential therapies involve drugs that target amyloid-beta, the sticky protein that accumulates in the brains of Alzheimer’s patients. In contrast, the new method used on mice causes certain nerve cells to fire at a specific rhythm, generating brain waves that researchers believe may clear A-beta.

“This is a very creative and innovative new approach to targeting brain amyloid load in Alzheimer’s,” says geriatric psychiatrist Paul Rosenberg of Johns Hopkins Medicine. But he cautions that the mouse results are preliminary.

Neuroscientist Li-Huei Tsai of MIT and colleagues saw that mice engineered to produce lots of A-beta don’t produce as many gamma waves in the hippocampus, a brain structure important for memory.  Using a method called optogenetics, the researchers genetically designed certain nerve cells in the hippocampus to fire off signals in response to light. In this way, the researchers induced gamma waves — rhythmic firings 40 times per second.

microglia versus amyloid-beta
CLEANUP CREW After stimulation that led to more gamma waves in a mouse’s hippocampus, immune cells called microglia (green) kicked into gear and began engulfing amyloid-beta (yellow). H.F. Iaccarino et al/Nature 2016
After just an hour of forced gamma waves, the mice had less A-beta in the hippocampus, the researchers found. Further experiments revealed that gamma waves packed a double whammy — they lowered A-beta by both reducing production and enhancing the brain’s ability to clear it.

Gamma waves kick off a series of brain changes that ultimately call microglia, a kind of immune cell, to action, the researchers suspect. After gamma waves were generated, microglia turned on genes associated with the cells’ job as scavengers, roaming the brain and engulfing offending particles including A-beta. Tsai and colleagues saw more microglia with A-beta inside after gamma waves had been induced with optogenetics.

Optogenetics involves genetic tweaks to make cells respond to light, a requirement that limits its use in people. But the researchers found another way to make gamma waves, one that doesn’t involve any genetic changes. Fast flickers of light caused nerve cells in the mice’s visual system to start firing rhythmically, creating gamma waves. And just as before, A-beta levels dropped in the brain area where gamma waves were created.

Scientists don’t know whether the gamma waves created in the mice’s visual systems might spread to — and potentially benefit — other brain areas, Tsai said December 6 in a news conference. It’s possible that visual stimulation might have a big effect in the brains of people, who rely on sight more than mice do, she said.

The visual flicker used on the mice isn’t uncomfortable, Tsai said. “You can hardly see the flicker itself,” she said, an attribute that may make the technology acceptable for people. Certain mental states, like those attained with meditation and heightened attention, are also known to induce gamma waves. Other researchers are exploring other types of sensory input to boost the brain’s gamma waves, including vibrating chairs.

Tsai and neuroscientist Ed Boyden, also of MIT, have founded a company that plans to test the technology on people. The similarities between the neural networks that make gamma waves in mice and people “gives us optimism to think about doing human trials,” Boyden said in the news conference. 

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