Light Clears Up Alzheimer's in Mice Like Brain Plumbing
When it comes to losing functional memory, slowing the rate of loss isn't enough, since remembering recent experiences and forming new memories is what separates us from most other forms of life. With this in mind, researchers tested a small, light-activated molecule in mice and successfully removed clumps of amyloid protein present in the brains of Alzheimer's patients, according to a new study published in the journal Brain.
While this is a long way from going to market for human applications, the technique could provide an alternative approach to immunotherapy — in addition to other uses treating other diseases associated with similar amyloids.
Light-activated catalyst destabilizes proteins linked to Alzheimer's symptoms
The research involved injecting the molecule directly into the brains of living mice suffering from Alzheimer's disease, followed by the use of specialized probes to shine light directly into the mice brains for 30 minutes per day, every day, for a week. The mouse brain tissue showed substantially reduced amyloid protein from the treatment upon chemical analysis. Additionally, further experiments with human brain samples donated from Alzheimer's disease patients seemed to support the potential of eventual use in humans.
"The importance of our study is developing this technique to target the amyloid protein to enhance clearance of it by the immune system," said Yukiko Hori, a University of Tokyo who was also co-first author of the newly-published research, in an embargoed report shared with Interesting Engineering. The tiny molecule developed in this research is called a photo-oxygenation catalyst, and seems to work against Alzheimer's disease in a two-part process.
It begins when the catalyst destabilizes the amyloid plaques via oxygenation (or adding oxygen atoms) — which causes a molecule to lose its stability by affecting the chemical bonds keeping its structure together. We also see this process in laundry detergents called "oxygen bleach." But unlike laundry detergent, this catalyst was created to specifically target the folded structure of amyloid and probably works via cross-linking specific parts of the molecule — known as histidine residues. The catalyst remains inert until it's activated externally via near-infrared light — which means future research could involve curating new ways of delivering the catalyst into the body via injection into the bloodstream, to reach target areas.
Future Alzheimer's disease treatment might involve just a shot and light
Once the catalyst is activated, immune cells in the brain called microglia remove the destabilized amyloid in a conventional process that clears out damaged cells and debris surrounding healthy cells. Observing mouse cells grown in a dish, the researchers witnessed the microglia eating up oxygenated amyloid, and breaking it down into acidic integral compartments of the cells.
"Our catalyst binds to the amyloid-specific structure, not to a unique genetic or amino acid sequence, so this same catalyst can be applied to other amyloid depositions," said Taisuke Tomita, a professor who led the new study at the University of Tokyo. This is significant because 4,000 people are diagnosed with diseases linked to amyloid outside the human brain — collectively called amyloidosis — according to the American Society of Clinical Oncology.
Combining light with a catalyst in a process known as photo-oxygenation is likely able to annihilate amyloid protein — whether or not it formed inside the body. And, while some types of Alzheimer's disease treatments successfully slow the formation of new amyloid plaques, the ability to eliminate plaques already coating human brains is crucial because amyloid starts to build up for years before the onset of initial symptoms — which means simply slowing the rate of growth can only delay the inevitable.
As of writing, the University of Tokyo team is attempting to modify their breakthrough catalyst design so they can activate it by shining a light through a human skull — which could work since this is near-infrared light, not visible wavelengths of our day-to-day lives. We're a long way from mass rollout of this technology, but this could hint at a future where keeping those suffering from Alzheimer's disease from losing memory function well into old age is as easy as injecting a catalyzer activated with a near-infrared light, pointed directly at one's head.
Researchers at Cedars-Sinai hospital in California have used single-neuron recording to discover two types of brain cells that establish boundaries between chunks of memory.