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Light and Alzheimer’s

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Flickering Light Mobilizes Brain Chemistry That May Fight Alzheimer’s

EXxcerpted from Georgia Tech News Center 02/03/2020


Sci-fi surrealness

Alzheimer’s strikes, with few exceptions, late in life. It destroys up to 30% of a brain’s mass, carving out ravines and depositing piles of amyloid plaque, which builds up outside of neurons. Inside neurons, phosphorylated tau protein forms similar junk known as neurofibrillary tangles suspected of destroying mental functions and neurons.

After many decades of failed Alzheimer’s drug trials costing billions, flickering light as a potentially successful Alzheimer’s therapy seems surreal even to the researchers.

Now, researchers have tapped into how the flicker may work. They discovered in the lab that the exposure to light pulsing at 40 hertz – 40 beats per second – causes brains to release a surge of signaling chemicals that may help fight the disease.

Though conducted on healthy mice, this new study is directly connected to human trials, in which Alzheimer’s patients are exposed to 40 Hz light and sound. Insights gained in mice at the Georgia Institute of Technology are informing the human trials in collaboration with Emory University.

The 40 Hz frequency stems from the observation that brains of Alzheimer’s patients suffer early on from a lack of what is called gamma, moments of gentle, constant brain waves acting like a dance beat for neuron activity. Its most common frequency is right around 40 Hz, and exposing mice to light flickering at that frequency restored gamma and also appears to have prevented heavy Alzheimer’s brain damage.

One of the surging signaling molecules, in particular, is associated with the activation of brain immune cells called microglia, which purge an Alzheimer’s hallmark – amyloid beta plaque, junk protein that accumulates between brain cells.


Immune signaling

In 2016, researchers discovered that light flickering at 40 Hz mobilized microglia in mice afflicted with Alzheimer’s to clean up that junk.  The new study looked for brain chemistry that connects the flicker with microglial and other immune activation in mice and exposed a surge of 20 cytokines – small proteins secreted externally by cells and which signal to other cells. Accompanying the cytokine release, internal cell chemistry – the activation of proteins by phosphate groups – left behind a strong calling card.

“The phosphoproteins showed up first. It looked as though they were leading, and our hypothesis is that they triggered the release of the cytokines,” said Singer, who co-led the new study and is an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory.

“Beyond cytokines that may be signaling to microglia, a number of factors that we identified have the potential to support neural health,” said Levi Wood, who co-led the study with Singer and is an assistant professor in Georgia Tech’s George W. Woodruff School of Mechanical Engineering.

The researchers will look for a causal connection to microglia activation in an upcoming study, but the overall surge of cytokines was a good sign in general, they said.


Chemical timing

The 40 Hz stimulation did not need long to trigger the cytokine surge.

“We found an increase in cytokines after an hour of stimulation,” Garza said. “We saw phosphoprotein signals after about 15 minutes of flickering.”

Perhaps about 15 minutes was enough to start processes inside of cells and about 45 more minutes were needed for the cells to secrete cytokines. It is too early to know.

The research team warns against people improvising light therapies on their own, since more data is needed to thoroughly establish effects on humans, and getting frequencies wrong could possibly even do damage.




PDF: J. NEUROSCI 2019; 10.1523/JNEUROSCI.1511-19.2019