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13 - 12 - 2016

Alzheimer’s : light – a new therapeutic hope

 Researchers from the Massachusetts Institute of Technology (MIT) have experimented with a non-invasive approach to treat Alzheimer’s disease: stimulation of neuronal activity using light. very encouraging preliminary results have been collected in mice.  

Alzheimer’s : light – a new therapeutic hope

Currently, most research on Alzheimer’s disease is aimed at finding a way to curb the progress of the disease, by developing molecules capable of slowing down the development of amyloid plaques in the brain of the patients. But the task is very complex and difficult to achieve.

Concretely, these amyloid plaques are an aggregation of beta-amyloid proteins. Agglomerates in plaques, these proteins become toxic to the nervous system, in particular by decreasing the connections between neurons. They are accused of being the cause of neurodegenerative diseases like Alzheimer’s.

But rather than attempting to intervene chemically on these plaques, MIT researchers have opted for another approach: to regulate the electrical activity of the brain. In a normal state, in the absence of Alzheimer’s, the network of neurons causes electrical waves called gamma waves, which are located between 20 and 50 hertz in frequency. But in the case of Alzheimer’s disease, the waves are disrupted.

To learn more, the researchers worked on genetically engineered mice that develop Alzheimer’s disease. They found that a decline in gamma waves occurred before the accumulation of beta-amyloid proteins


Light to decrease the level of beta-amyloid proteins


To restore a suitable level of gamma waves, the scientists used optogenetics. This technique allows the stimulation in a fast and targeted manner, precise zones and neurons made sensitive to light by genetic modification. Adjusted to a frequency of 40 Hertz, this luminous stimulation reduced by 40 to 50% the levels of beta-amyloid proteins. Note that stimulations at other frequencies, between 20 and 80 Hertz did not achieve this result. However, optogenetics remains an invasive approach, since it requires surgery to install an optical fibre directly into the brain. The team has developed another, less invasive technique, using a kind of stroboscope, consisting of several LEDs that blink and are sent at 40 Hertz (see video). 

A first group of mice, exhibiting an excess of beta-amyloid proteins but not yet formed into plaques, were exposed for one hour to these flashing LEDs. This exposure was enough to halve the amount of proteins, but they returned to their original amount within 24 hours.

The second group of mice, already showing amyloid plaques in the brain, was exposed to LED light for one hour a day for seven days. As a result, the plaques decreased significantly. How long this effect will last, still remains to be studied.  





A technique that will need to be proven in humans


“What this study allows us to do, (…) is to show that gamma waves, known for a long time, are linked to cognitive function and play a crucial role in the brain’s ability to clear deposits”, explained Alvaro Pascual-Leone, a professor of neurology at Harvard Medical School, who commented the research on the MIT website. “It is remarkable and surprising, and it opens tremendous prospects for a possible application in humans.”

But it will be challenging to achieve the same results in humans, it is not obvious. Li-Huei Tsai, a neuroscience researcher and principal author of the study, expresses some reservations, commenting that sometimes studies work well in mice but fail in humans. “ But if the response to this treatment in humans is the same as in mice, I would say that the potential is simply enormous, because it is non-invasive and very accessible”, she concluded on a more optimistic note. 



Mice, the preferred model to study Alzheimer’s disease


This study, published in Nature on December 7, was conducted in mice, and this isn’t only because they are an easy model to breed in the lab. Mice are mammals that have great similarities with humans, both genetically, immunologically, physiologically and pathologically. Easily modified genetically, mice are used as a model for many diseases. A new mouse model for Alzheimer’s disease was developed in February 2016, and allows the study of early stage Alzheimer’s disease, that is to say, the stages before the appearance of amyloid plaques. It is a prime model to study the initial damages of this degenerative disease and its evolution over time. 


Hélène Bour


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