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LEDs Shown to Reduce Alzheimer’s Brain Plaques

Li-Huei Tsai

Li-Huei Tsai (Massachusetts Institute of Technology)

8 December 2016. Pulsating LED lights were shown in lab mice to reduce amyloid-beta plaque deposits associated with Alzheimer’s disease on brain cells. A team from Massachusetts Institute of Technology reports its findings in the 7 December issue of the journal Nature (paid subscription required), with the senior authors starting a company to commercialize the technology.

Researchers from the labs of MIT neuroscientist Li-Huei Tsai and bioengineering professor Edward Boyden are seeking alternative treatments for Alzheimer’s disease, a progressive neurodegenerative disease affecting growing numbers of older people worldwide. People with Alzheimer’s disease often have deposits of abnormal substances in spaces between brain cells, known as amyloid-beta peptides, as well as misfolded tangles of proteins inside brain cells known as tau. The Alzheimer’s Association says some 5.4 million individuals in the U.S. have the disorder, of which 5.2 million are age 65 or older.

In this study, Tsai, Boyden, and colleagues explored the relationship between gamma oscillations, rhythmic neural signals in the brain, and the build-up of amyloid-beta plaques. Gamma oscillations are believed to help the brain perform normal functions, including perception and memory, but previous research also indicates gamma oscillations may be impaired in people with Alzheimer’s disease.

The team examined these connections in genetically engineered mice to express Alzheimer’s disease. While the mice did not yet have amyloid-beta plaques built-up in their brains, they still showed impaired gamma oscillations. Using techniques from optogenetics, the use of light energy to influence activities of genes sensitive to light, researchers were able to stimulate gamma oscillations at 40 Hz, or cycles per second, in the hippocampus region of the brain important to memory formation and retention. An hour of stimulation at 40 Hz — and only 40 Hz, higher and lower frequencies did not work — showed a 40 to 50 percent reduction in amyloid-beta plaques in the hippocampus regions of the test mice.

Current optogenetics techniques use implanted circuits to generate the energy to influence light-sensitive genes, and the team sought a less invasive alternative. The researchers turned to MIT bioengineering colleague Emery Brown who devised a panel of light-emitting diodes, or LEDs, to flicker at specified frequencies. Exposing genetically engineered mice to an hour of these flickering LEDs at 40 Hz showed gamma oscillations increased in the visual cortex of their brains, the part of the brain that processes visual information, and also reduced beta-amyloid deposits by about half.

The lower amyloid-beta peptides did not last, however, and within 24 hours returned to their original levels. The researchers then exposed test mice with plaque deposits to daily one-hour treatments of flickering LEDs for 7 days and found sharply reduced amyloid-beta levels in the visual cortex, as well as misfolded tau protein deposits also associated with Alzheimer’s. The team discovered as well that enhanced gamma oscillations result in more active immune system cells known as microglia that clear out beta-amyloid peptides from the brains of the test mice.

“The bottom line is, enhancing gamma oscillations in the brain can do at least two things to reduced amyloid load,” says Tsai in an MIT statement. “One is to reduce beta-amyloid production from neurons. And second is to enhance the clearance of amyloids by microglia.”

Results from these initial tests are providing a road map for further examinations into the length of time beta-amyloid deposits can be reduced, other regions of the brain outside the visual cortex that can be treated, effects on behavior of treated mice, and potential for other neurological disorders associated with reduced gamma oscillations.

Even while these further explorations go on, Tsai and Boyden founded the company Cognito Therapeutics in Newton Centre, Massachusetts to develop treatments for neurodegenerative diseases based on their research, leading to clinical trials. As reported in the Boston Globe, Cognito Therapeutics is being formed at TheraNova LLC, a medical device incubator in San Francisco, but plans to return its operations to Massachusetts. Morningside Ventures, a Hong Kong investment firm, is providing the company’s initial venture funds.

The following video tells more about the research.

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