Most strategies for treating Alzheimer’s disease center on finding a drug that will reverse the disease pathology biochemically. Drugs, however, can be expensive and have side effects, and so far none have worked.

In 2016, the labs of Li-Huei Tsai, Emery Brown and Ed Boyden teamed up to try a completely different approach: After observing that gamma frequency (40Hz) brain wave power and synchrony is substantially weaker in Alzheimer’s model mice and may also be in patients, they experimented in mice with instilling the rhythms with completely non-invasive 40Hz flashes of visible light. In a paper in Nature in December 2016, they showed that the flashes had several beneficial effects: it reduced amyloid beta plaques in the visual cortex both by reducing their production and by stimulating microglia to clear the plaques away.

The trio called this non-invasive, inexpensive potential treatment for neurodegeneration: GENUS, for Gamma ENtrainment Using Sensory stimuli. In 2019 in Cell they showed that 40Hz sound stimulation works in mice, too, and in a paper in Neuron they showed that long-term GENUS light protected against neurodegeneration. Both papers showed that GENUS preserved memory and cognitive performance, too. They have since begun testing GENUS in humans with early, but encouraging, results. Tsai and Boyden also founded the company Cognito Therapeutics to accelerate this translational work. They are also studying whether non-invasive entrainment of rhythms can positively impact other diseases and partnering with engineers and designers to invent new modes for delivering the stimuli.

Above: A rendering of a microglia-like cell, stimulated to action by GENUS, absorbing amyloid plaques.