Category Archives: Neurodegenerative Disease

Blinking Lights Used To Treat Alzheimer’s Disease In MIT Study. How Does This Even Work?

The Study

Recently, MIT released a study showing evidence that mice bred to have Alzheimer’s disease, when exposed to blinking LEDs at 40hz, had their amount of illness causing amyloid-beta protein reduced. The effect even worked in “Wild Type” mice that were not specifically bred to exhibit Alzheimer’s symptoms.  The effect prevented amyloid-beta build up in mice in the early stages of the disease, but it also reduced amyloid-beta protein in mice that had already accumulated significant amounts of the protein and were thus at a later stage of the disease.  This result seems hard to make sense of because flashing lights aren’t something that seems capable of having disease curing effects. How could this possibly work given the difficulty in treating neurodegenerative diseases?

Looking more closely at the study, specifically at the mechanism of action proposed by the researchers, we find increased microglial activity. The microglial cells are the primary immune system cells in the brain. Some theorize that infections cause Alzheimer’s in the brain, so according to that theory, increasing the activity of microglia could help fight a possible Alzheimer’s disease causing infection.  In the study, the specific observed activity of the microglia was an increase in engulfing of amyloid beta proteins.  The end products of degraded amyloid protein were also reduced.  This suggests that there was an alteration in endosomal processing.

When researchers blocked GABA receptors, the amyloid clearing effect no longer worked. Contradicting GABA receptor activation being the sole source of the amyloid-beta reducing effect is that in the past GABA agonists failed to improve Alzheimer’s patient’s outcomes.

Speculation

GABA receptors connect to microglia via astrocytes. Astrocytes modulate microglial activity, and their behavior is affected via GABA signaling. GABA acts as an anti-inflammatory via these cells. Strengthening the anti-inflammatory hypothesis is there is evidence that anti-inflammatories such as aspirin protect against Alzheimer’s pathology.

Astrocytes are related to circadian rhythm brain entrainment and Gamma oscillations. Flicking lights on and off increases glutamate signaling which is countered by GABA signaling from astrocytes. If GABA signaling doesn’t modulate glutamate signaling, that leads to the well known human photoparoxysmal response in people with epilepsy, in which blinking lights can cause seizures, perhaps because of sclerotic astrocytes that can’t function properly to slow down the elevated glutamate driven excitation.

So can we spin together a theory about how this all works? How do blinking lights reduce disease causing amyloid plaques?

My Speculation: Blinking lights cause astrocytes to get activated and release GABA to control photoparoxysmal driven glutamate signaling. This release, along with other signals from astrocytes, triggers anti-neuroinflammation and engulfing activity in microglia which helps clean up Alzheimer’s damage. Lack of effectiveness of GABA agonists alone in the treatment of Alzheimer’s disease provides evidence against the idea that GABA alone was solely responsible for the effect. Perhaps there is some other necessary signal that is released by astrocytes along with GABA to influence microglial anti-inflammatory behavior.

Researchers have linked neuroinflammation to other neurodegenerative diseases, so the applicability of this mechanism of action could be widespread.