Alzheimer’s disease, it's one that hits too close to home for many of us. It is an awful experience to watch as one of our loved ones undergoes the slow cognitive decline associated with this disease. At first they struggle to remember how to travel to your home, then they can’t remember how to do simple tasks like cook food, or wash clothes. In the blink of an eye, they forget who their loved ones are, forget their children, and (if they have them) grandchildren.

This awful disease has been under the scientific spotlight for quite some time, and as a result we have discovered many things about why it develops, however how to effectively treat it has largely remained elusive. Recently, one group of MIT researchers has shined a light on the disease (literally) and their results should give us all hope. The authors discuss their findings in a recent publication in the journal Nature titled “Neurodegenerative disorders: Neural synchronization in Alzheimer’s disease.”

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A Bit of Background on Alzheimer’s Disease

Alzheimer’s is a neurodegenerative disease, and like many diseases of this variety it slowly results in the death of brain cells. When you have Alzheimer’s disease, your brain literally shrinks and the amount of nerves present decreases. The death of brain cells and loss of neuronal functioning is what leads to the outward symptoms of dementia (aka memory loss) that is so characteristic of this disease. But why does this happen?

Beta-Amyloid Plauqes

In your brain you have a lot of neurons, which are cells responsible for transmitting the electric signals that allow our brains (and central nervous system) to function. The tissue that surrounds these neurons is composed of fat and a protein called an Amyloid Precursor Protein. This is an integral membrane protein (which means it is a part of the cellular membrane, permanently, they do not come and go, they are affixed). The actual function of this protein is not currently known, however it is hypothesized to regulate synapse formation (synapses are the gaps between neurons). Now these amyloid precursor proteins CAN get cleaved by a protein called beta secretase. Beta secretase is a protease (aka a protein which cuts other proteins) that is essential for the formation of the myelin sheaths of nerve cells. Myelin is what insulates the nerves and allows the electric impulses they transport to move freely through the cells.

So there is a site on the amyloid precursor protein that the beta secretase can chop at, if it does this it released a small protein chunk called Beta Amyloid:

Source: Beta Amyloid

These small protein chunks can clump together or aggregate. They do this because they are not folded correctly, aka their shape just isn’t right. When beta amyloid aggregates form, they form large clumps called plaques:

Source: See that large brown blob on the right hand side of this electron microscopic image of Alzheimer’s brain tissue? That brown spot is a beta amyloid plaque

When these plaques form they can have a few detrimental effects, they can block the signaling between neurons (bad) and they can cause an immune response that results in the “misfiring” neurons to get attacked and destroyed (worse!).

Other Issues: Impairment of Gamma Oscillations

In addition to the aforementioned beta amyloid plaques, studies have indicated that people who suffer from Alzheimer’s disease also have an impairment in a particular “brain wave” AKA pattern of neuronal firing. This pattern that gets disrupted in Alzheimer’s patients is called a gamma oscillation:

Source: Gamma Oscillation

This type of brain wave occurs at a frequency between 25 and 100 Hz (Hertz is oscillations per second). Gamma oscillations are thought to somehow be involved in creating awareness, however there is no real agreement on that so to speak.

So What Did The Researchers Find Out About The Light?

Okay, so we are refreshed a bit on some of the underlying issues that lead to the onset of Alzheimer’s disease. In the performed experiments the authors were testing on a variety of mice (5XFAD) which are engineered to develop Alzheimer's disease. These mice all have reduced levels of gamma oscillations and high amounts of beta amyloid plaques.

What the authors have reported is that by exposing the mice to LED’s flashing at 40 Hz for just one hour, resulted in noticeably reduced amounts of amyloid beta levels for up to 24 hours. The authors then repeated these one hour treatments every day for seven days. Upon doing this they found dramatically reduced levels of the beta amyloid plaques in the visual cortex (the part of the brain responsible for processing visual stimuli… aka it translates what your eyes see into brain speak). The authors performed control experiments using other light flickering patterns and saw no effect. Therefore the flickering in the 40 Hz pattern, resulting in the uptick in brain gamma oscillations directly resulted in the reduction in the beta amyloid plaques.
*NOTE that the visual cortex is not effected in standard Alzheimer's sufferers, and only contains plaques in these mice as they are artificially induced to have them in all parts of their brains. So this particular light flashing technique is not directly usable as a treatment for humans with the disease.

This is a fascinating result, and shows that brain cells are able to clear the amyloid beta plaques in response to patterns of activation of neurons. Now the work will have to continue to determine an explanation of why this happens (that is science after all... answering those WHY questions). If these stimulation's result in the release of neuronal compounds responsible for the breakdown of the plaques, there could be some very effective therapeutics developed (to look at this from Pharma's perspective). At the very least, this result is very promising, and illustrates the potential for simple beneficial treatments for current Alzheimer’s sufferers. If stimulation of these gamma oscillations allow neurons to clear the plaques, perhaps there are ways to stimulate these brain waves over the entire brain, rather than just the visual cortex. Hopefully work will continue, it would truly be amazing if a non-invasive, simple solution to this terrible disease could be found. So many people’s lives could be improved. So many families restored.

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Sources:

http://www.nature.com/nature/journal/v540/n7632/full/540207a.html
http://www.medicalnewstoday.com/articles/159442.php
https://en.wikipedia.org/wiki/Amyloid_precursor_protein
https://www.alz.org/braintour/plaques.asp
https://en.wikipedia.org/wiki/Gamma_wave

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