Alzheimer’s: the attractive avenue of visual and auditory stimulation to “clean” the brain

Could simple visual and auditory stimulation slow the progression of Alzheimer's disease? Or to put it even more simply, could sound and light succeed where so many drugs have failed? This is a hypothesis that has been in vogue for several years, but is still debated in the scientific community. Experimental data, published in the journal Nature on February 28, nevertheless provide new convincing elements in favor of this “sensory gamma stimulation”, which is still little known.

The person who led this work is none other than Li-Huei Tsai, professor at the Massachusetts Institute of Technology (Boston – United States) and director of the Picower Institute for Learning and Memory. This specialist in Alzheimer's disease has been working for around ten years on the cerebral effects of sensory stimulation, particularly in neurodegenerative diseases. She conducted the first studies on the subject by directly stimulating the visual and auditory cortices in the mouse brain. His team had shown that stimulation of these brain areas at the precise frequency of 40Hz was the most effective, a result which has since been reproduced. This frequency corresponds to that of gamma waves produced by the brain in moments of intense concentration, when we are absorbed in an exciting conference or working on a complex project.

But what does this have to do with Alzheimer’s? It is the “glymphatic” system that would be blamed. “The lymphatic system has been known for a long time,” recalls Philippe Amouyel, professor of public health at Lille University Hospital and director general of the Alzheimer Foundation. “But lymph bathes all organs except the brain. In 2012, the work of Danish researcher Maiken Nedergaard showed that it had a sort of local lymphatic system whose functioning relies in part on glia cells (a set of cells that surround neurons in the brain, Editor's note). , hence the name glymphatic. »

Like the lymphatic system, the glymphatic system plays a cleaning role. This circuit would allow waste produced by the functioning of brain cells to be collected in the interstitial fluid and then eliminated. Among these wastes there is notably the β-amyloid protein, the abnormal accumulation of which is associated with Alzheimer's disease. Multisensory stimulation would therefore improve glymphatic function, and thus the elimination of the protein.

In this new publication, the researchers tested the effectiveness of stimulations, but this time in a non-invasive way: the animals were exposed to sounds and flashes of light. The data show that external stimulations at 40Hz are the most effective in improving the elimination of ß-amyloid protein. On the other hand, researchers show that by blocking the action of certain cellular transporters considered to be key elements of the glymphatic system, sensory stimulation no longer has an effect. Stimulations at 40 Hz would also increase the production of a neuropeptide which acts on the contractility of small arteries, which would intensify exchange flows with the glymphatic system and improve drainage of the brain.

Can these experimental results fuel any hope for therapy? “You have to be very careful,” recommends Jean-Léon Thomas, professor in the department of neurology at Yale University (Connecticut, United States) and at the Brain and Spinal Cord Institute (ICM), in Paris. The discovery of the glymphatic system is very recent, and although attractive and already well supported, it still generates a lot of debate in the scientific community. » Some skeptics point out, for example, that these experiments require tracers whose very injection could modify the pressure in the glymphatic system, which would distort the results.

“There has been real enthusiasm in recent years for brain stimulation in different forms for different indications,” notes Professor Amouyel. We can easily imagine that such results, obtained with a technique apparently devoid of adverse effects, could fuel the desire of certain companies ready to offer helmets to “protect against Alzheimer's” without having previously evaluated them in a comparative clinical trial. » However, caution must be exercised, particularly in this pathology. “Unfortunately, we have observed several times that drugs which seemed effective in mice turned out to be much less convincing in humans,” recalls the doctor. In this case, these latest experiments were, for example, only carried out on a mouse model that “mimics” only one type of development of Alzheimer's disease. And the few trials carried out so far on humans are not of sufficient quality to allow us to conclude that there is any therapeutic benefit from these sensory gamma stimulations.

The US military seems to be much quicker to move from mouse to man. Since 2021, it has funded a research program led by Rice University to develop a helmet that stimulates the activity of the glymphatic system in order to improve cleaning of soldiers' brains... while they sleep.