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Longevity Briefs: Could We Treat Alzheimer’s Using Only Light And Sound?

Posted on 5 April 2024

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem: Relatively recently, scientists discovered an entirely new system in the brain called the glymphatic system. It’s a space that surrounds blood vessels in the brain and allows cerebrospinal fluid (CSF) to pass alongside them. As blood pulses through the arteries, fresh CSF is pushed into the brain tissue, filtering through brain cells and effectively washing waste products out of the brain via the veins. This glymphatic system becomes less effective at clearing waste with age, resulting in the build up of waste products like amyloid, which is involved in Alzheimer’s disease.

Representational diagram showing the structure of the glymphatic system. Waste products from neurons enter the interstitial fluid (ISF) and are washed into the space surrounding the veins.
The glymphatic system: a new perspective on brain diseases

In a previous study, researchers used optogenetics (a genetic technique allowing scientists to control the activity of brain cells using light) to show that enhancing certain types of brain waves boosted the clearance of waste by the glymphatic system in animals. Specifically, they found benefit in gamma waves, which are typically dampened in Alzheimer’s patients. Gamma waves are fast brain waves associated with higher cognitive functions and with dreaming, and occur when many brain cells fire in synchrony at a rate of 30 firings per second or more. In this study, the researchers wanted to see if they could enhance gamma waves and promote amyloid clearance using only noninvasive techniques.

The discovery:

Researchers found that they could promote waste clearance by the glymphatic system in mice simply by exposing them to visual and auditory stimuli with frequencies of 40 Hertz (40 repetitions per second). They used a genetic mouse model that produces high amounts of amyloid and rapidly develops a mouse version of Alzheimer’s disease, and divided them into groups ranging in size from 4 mice to 10. They then exposed one group of mice to 40 Hz auditory tones and a 40 Hz flashing LED light, simultaneously, for one hour. Other groups were exposed to either 8 Hz or 80 Hz, while one group was left as a control and did not receive the treatment. They found that the presence of amyloid within the cerebral cortex was significantly reduced in mice receiving 40 Hz stimulation, but not in any of the other groups, and that this was linked to an increase in flow of cerebrospinal fluid via the glymphatic system.

Images showing amyloid presence within the frontal cortex in mice treated with different frequencies. The blue regions are dense cores of amyloid, while the grey regions are less dense ‘halos’ of amyloid.
Multisensory gamma stimulation promotes glymphatic clearance of amyloid

What caused this increased glymphatic clearance? The researchers found that 40 Hz frequencies induced gamma waves in certain neurons, causing them to release a signalling molecule called VIP (vasoactive intestinal peptide). This was linked to an increased pulsation in the cerebral arteries, which drives cerebrospinal fluid through the glymphatic system. They also detected changes in gene expression in astrocytes. Astrocytes are the ‘gatekeepers’ of the glymphatic system, overseeing the passage of molecules between the brain tissue and the spaces in between the blood vessels. They found that with 40 Hz stimulation, astrocytes increased their expression of channel proteins that facilitate the flow of fluid into and out of the brain tissue, presumably aiding the clearance of amyloid protein.

The implications:

This is quite an exciting discovery, suggesting that noninvasive exposure to light and sound is enough to promote the clearance of amyloid and probably other harmful waste from the brain. The conditions in this study could be replicated with ease and may have the potential to treat or prevent Alzheimer’s disease, age-related cognitive decline, and perhaps improve cognitive function even in the absence of disease. 

With that being said, mouse studies of Alzheimer’s disease need to be taken with a pinch of salt. Alzheimer’s in humans is linked to a gradual accumulation of amyloid over decades, while the mice in this study were genetically engineered to produce high levels of amyloid so that they developed Alzheimer’s-like problems within 6 months. The importance of amyloid plaque in human Alzheimer’s disease may also vary from person to person, and the researchers did not test whether the treatment actually improved the mice’s’ cognitive function, so it’s far too early to draw any conclusions about the implications for human health. Another experiment the researchers didn’t do was to test the treatment in normal mice that weren’t genetically engineered to develop amyloid disease. As a result, we don’t have any indication of whether 40 Hz frequencies would increase glymphatic clearance in healthy mammals, which might have implications for general health, cognition and wellbeing. Based on other studies, it does at least seem as though gamma brain waves can be induced in humans through simple sensory stimulation, and there is even some early research showing that this is beneficial for Alzheimer’s patients.

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    Title image by djvstock on Freepik

    Multisensory gamma stimulation promotes glymphatic clearance of amyloid

    Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies

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