Power of light and oxygen removes Alzheimer’s protein in live mice

A small, light-activated molecule recently tested in mice represents a new approach to eliminating clumps of amyloid proteins found in the brains of Alzheimer’s patients. When perfected in humans, the technique can be used as an alternative approach to immunotherapy and is used to treat other diseases caused by similar amyloids.

Researchers injected the molecule directly into the brains of live mice with Alzheimer’s disease and then used a specialized probe to shine light in their brains for 30 minutes every day for one week. Chemical analysis of the mouse brain tissue showed that the treatment significantly reduced amyloid protein. Results of additional experiments using human brain samples donated by patients with Alzheimer’s disease support the possibility of future use in humans.

“The importance of our study is to develop this technique to target the amyloid protein to enhance its clearance by the immune system,” said Yukiko Hori, a lecturer at the University of Tokyo and co-author of the research recently in Brain.

The small molecule that the research team developed is known as a photooxygenation catalyst. It appears to treat Alzheimer’s disease through a two-step process.

First, the catalyst destabilizes the amyloid plates. Oxygenation, or the addition of oxygen atoms, can make a molecule unstable by changing the chemical bonds that hold it together. Detergents or other cleaning agents, known as oxygen bleach, use a similar chemical principle.

The catalyst is designed to direct the folded structure of amyloid and probably works by crosslinking specific portions called histidine residues. The catalyst is inert until it is activated with near-infrared light, so in the future, researchers may suggest that the catalyst can be delivered through the body by injecting into the bloodstream and targeting specific areas with light.

Second, the destabilized amyloid is then removed by microglia, immune cells of the brain that remove damaged cells and debris outside healthy cells. Using mouse cells growing in a dish, researchers observed that microglia swallow oxygen-like amyloid and then break it down into acidic compartments in the cells.

“Our catalyst binds to the amyloid-specific structure, not to a unique genetic or amino acid sequence, so the same catalyst can be applied to other amyloid deposits,” said Professor Taisuke Tomita, who led the project at the University of Tokyo.

The American Society of Clinical Oncology estimates that in the United States, 4,000 people are diagnosed annually with diseases caused by amyloid outside the brain, collectively known as amyloidosis. (www.cancer.net/cancer-types/amyloidosis/statistics)

The photooxygenation catalyst must be able to remove amyloid proteins, regardless of when or where they are formed in the body. Although some existing treatments for Alzheimer’s disease may delay the formation of new amyloid plaques, removal of existing plaques is especially important in Alzheimer’s disease, as amyloid begins to contract years before symptoms appear.

The research team is now changing the design of the catalyst so that it can be activated by shining light through the skull.

This research is a peer-reviewed experimental study using mice and human tissue samples. Human temporal cortex brain samples used in this research are from the Alzheimer’s Disease Core Center (ADCC) and the Center for Neurodegenerative Disease Research (CNDR) at the University of Pennsylvania in the USA.