8 | Health
Gamma band stimulation A promising new treatment for Alzheimer’s
BY DINA ZEMLYANKER, DATA SCIENCE & BIOCHEMISTRY, 2024
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DESIGN BY VICTORIA PAJAK, BEHAVIORAL NEUROSCIENCE, 2021
lzheimer’s disease is a vicious illness most often of 5XFAD/PV-Cre mice that model Alzheimer’s. APP characterized by drastic decline in cognitive determines brain amyloid concentration, and is the function including memory loss and confusion — precursor to Aβ; the more cleavage of APP that occurs, the frequently causing severe emotional stress for the affected greater the brain amyloid concentration, a pathological along with their family and friends. Fortunately, recent marker of Alzheimer’s. After the 40 Hz stimulation, there technology, called gamma band neural stimulation, has was a significant reduction in C-Terminal and N-Terminal emerged, showing promise of having a significant impact fragments showing less cleavage of APP. Experts also on Alzheimer’s. Although the direct causes and mechanisms concluded that the stimulation decreases endosomal by which Alzheimer’s affects people are not fully known, processing of APP, as they documented a decrease in the there are several viable hypotheses that have been found to markers for endosomes (early antisomnal antigen 1 and Rashave merit. The common key pathological understanding related protein). between all of them is that extracellular deposits of amyloid-β (Aβ), and intracellular neurofibrillary tangles (NFT) of tau, The 40 Hz stimulation also caused changes in the state of which is a protein that helps create structures that transport microglia, which are brain and spine cells that act as immune nutrients in nerve cells, are defense for the central the main markers and causes nervous system. Researchers of visible symptoms. The observed that 35 percent of Although the direct causes most common hypothesis, the the upregulated genes, or amyloid hypothesis, posits that genes expressed at higher and mechanisms by which mutations in genes coding for rates due to the stimulation, Alzheimer’s affects people amyloid-β precursor protein had the highest expressions (AβPP), a protein metabolized in microglia. Almost twice as are not fully known, there are to breakdown products, and many microglia were observed several viable hypotheses.” presenilin peptides, which in the 40 Hz group compared to form catalytic subunits in the control groups. In addition, gamma secretases which also breakdown proteins, result microglia cell body diameter increased by 138.7 percent in less efficient AβPP catabolism. This in turn leads to Aβ compared to random stimulation. Given that microglia act as oligomer aggregation forming insoluble Aβ plaques. This the main defense for the brain, an increase in the amount and causes synaptic damage and destructive inflammation, along size of microglia suggests that the 40 Hz stimulation leads to with the phosphorylation of tau, which all lead to cognitive a more effective brain defense system as well as decreased dysfunction and dementia. Aβ plaque accumulation.
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Currently, the only pharmacologic treatments are acetylcholinerase inhibitors and N-methyl-D-aspartate receptor antagonists. Experts based the inhibitors on the cholinergic hypothesis, meaning that the medicine mimics the natural role of acetylcholine as a neurotransmitter in the brain. Unfortunately, these treatments can only slow the progression of the disease by around 30 percent and cannot prevent nor cure Alzheimer’s. However, gamma band neural stimulation shows promise to significantly impact the disease. During sensory information processing and cognitive memory tasks, gamma activity increases in the brain. A reduction in gamma power occurs in people with Alzheimer’s even before there is a visible accumulation of plaque or amyloid protein. In an experiment done by Iaccarino et al, 40 hertz brain stimulation was shown to have significant positive effects. The levels of amyloid precursor protein (APP) intermediates (C-Terminal and N-Terminal fragments) were measured to examine the effects on the APP cleavage in the hippocampus
Visual stimulation has also been shown by the same researchers to be an effective method of Aβ level reduction. After 3-month-old 5XFAD mice were exposed to 40Hz visual light stimulation using white lights, Aβ1-40 and Aβ1-42 levels were respectively reduced by 57.96 percent and 57.97 percent compared to the dark controls. The light stimulation traveled through the retina and optic nerve and resulted in increased gamma activity in the visual cortex, which led to the reduced Aβ levels. Although there is still much more research to be done, especially regarding the effects of gamma stimulation on humans and not just mice, gamma stimulation has emerged as one of the first treatments with the potential to treat Alzheimer’s effectively. Instead of just mildly ameliorating some of the symptoms, it may be able to treat already developed Alzheimer’s and even stop the disease from progressing. Journal of Alzheimer’s Disease (2018). DOI:10.3233/JAD-180391 Nature (2016). DOI:10.1038/nature20587