Gamma Frequency Entrainment Attenuates Amyloid Load and Modifies Microglia

Iaccarino H, Singer A, Martorell A, et al. Nature. 2016.

Alzheimer’s Disease (AD) is classified as a chronic neurodegenerative disease and is the most common form of dementia with 5 million cases in the US alone. Although it is not fully known what causes AD, researchers are beginning to find correlations between decreased brain oscillations and AD.

Brain oscillations are broken down into different frequencies, including the gamma frequency which ranges from 35-100 Hertz (Hz). During AD, brain oscillations have been shown to change. The researchers in this study thought that if they could somehow artificially stimulate the gamma frequency in a patient with AD back to normal levels, this could slow or possibly reverse the effects of AD. They designed a study where mice had a fiber optic cable placed through the skull and into the brain.Each test subject received one of three stimulations: 8 Hz, 40 Hz, or a random stimulation. Researchers looked at amyloid beta levels in the hippocampus of the mice after the simulations. While 8 Hz and random stimulation did not produce significant results, 1 hour of stimulation at 40 Hz reduced two distinct amyloid beta levels by 53.22% and 44.62% and increased microglia activity. Researchers wanted to recreate similar outcomes, but in a less invasive study that could possibly be recreated on a human patient. The thought was that instead of introducing the stimulus directly into the brain, could they recreate the experiment by having the stimulus come through the eyes as a visual stimulus. The mice were then placed in a dark room and exposed to one of five different stimulations: dark, light, 20 Hz, 40 Hz, or 80 Hz. Although all other groups were not significantly different, one hour of 40 Hz flicker reduced distinct amyloid beta levels by 57.96% and 57.97%. Researchers also looked at microglia activity after 1 hour in a 40 Hz flicker room. Results showed that the microglia count had stayed constant, but microglia cell body diameter increased by 165.8%, which they concluded indicates boosted phagocytic activity. The final part of the study considered how light flicker effects amyloid plaques. Interestingly enough, after I hour of 40 Hz flicker, the plaques were reduced in size by 63.7% and decreased in number by 67.2%. Plaques began to return to normal size along with lowered microglia activity after the mice would not receive the flicker treatment for multiple days. 

The research concluded that it is possible to slow the effects of AD temporarily in mice, but the results from the flicker test show a non-invasive treatment that might be possible on a human patient and may lead to a new form of therapy for Alzheimer’s Disease in the future.

I came across this article after reading a few other papers that stated hypertensive rats showed increased levels of activated microglia in the rostral ventrolateral medulla (RVLM). I wanted to understand the role of microglia in the other parts of the brain before I compared it to their role in the RVLM.

Paul M