Treating Alzheimer’s With Sound

This piece, by Onno Berkan, was published on 02/11/25. The original text, by Murdock et al., was published by Nature on 02/28/24.

This MIT study investigated a promising non-invasive treatment approach for Alzheimer's disease that uses synchronized light and sound stimulation. The researchers focused on specific brain wave patterns called gamma oscillations, which occur at 40 Hz, and their potential role in clearing toxic proteins from the brain.

The study built upon previous research showing that light flickering at 40 Hz could reduce amyloid proteins in mouse models of Alzheimer's disease. In hopes of making the treatment more effective, the researchers combined both light and sound stimulation at 40 Hz. This multisensory approach increased beneficial brain activity across multiple brain regions and reduced harmful amyloid proteins.

A key discovery was understanding how this stimulation helps clean the brain. The researchers found that the 40 Hz stimulation enhanced the brain's natural cleaning system, called the glymphatic system. This system acts like the brain's waste removal service, using cerebrospinal fluid to flush out harmful substances. The treatment worked in several ways: it increased the flow of cleaning fluid into the brain, improved the function of specialized water channels in brain cells (called aquaporin-4), and helped dilate the lymphatic vessels that drain waste from the brain. 

Disappointingly, we do not know why this 40 Hz stimulation activates the glymphatic system.

Accepting the stimulation's effects, the researchers verified that these effects were specifically tied to the 40 Hz frequency. They didn't see the same beneficial effects when they tested other frequencies (8 Hz and 80 Hz). They also confirmed that the improvements weren't simply due to changes in sleep patterns or stress levels, suggesting that the treatment worked through specific biological mechanisms.

The researchers investigated the role of special brain cells called VIP interneurons to understand the effectiveness of the treatment. Their findings showed that these cells were crucial for its success, as they helped regulate blood vessel pulsing, which is important for the brain's cleaning process. When these cells were blocked, the treatment became less effective at removing amyloid proteins.

The findings are particularly exciting because they reveal multiple ways gamma stimulation helps clear harmful proteins from the brain. While most of the brain's cleaning typically happens during sleep, this research suggests that the cleaning process can be enhanced in the awake brain through targeted stimulation. This is especially promising because it offers a potential noninvasive treatment approach that could help address one of the fundamental problems in Alzheimer's disease: the accumulation of toxic proteins.

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