A new imaging probe that could help to advance therapies for Alzheimer’s disease draws its inspiration from an unlikely source.
Research suggests that Alzheimer’s is closely associated with increased levels of ‘reactive oxygen species’ (ROS) in the brain, but actual, in vivo evidence of this has proved scarce. Now, the Martinos Center’s Chongzhao Ran and colleagues have looked to glow sticks—those luminescent plastic tubes favored by survivalists, ravers, and young children on a warm summer’s night—in developing a means to detect and monitor ROS.
Here’s how it works. In a glow stick, oxalate and hydrogen peroxide—a reactive oxygen species—are loaded into separate compartments. When you bend the stick, the barrier between the compartments breaks and the substrates are allowed to mix. The resulting chemical reaction produces the temporary luminescence. Similarly, in the imaging probe designed by Chongzhao and colleagues, oxalate reacts with ROS in the brain to produce a shift in the wavelength of the probe. The researchers can detect this shift with the imaging technique two-photon microscopy, thus making quantification of the ROS possible.
This opens up a number of opportunities in Alzheimer’s research. Using the probe could yield reliable information about the changes in ROS concentrations both in the natural progression of the disease and in the wake of treatment. “The data could be very important to determine whether anti-oxidants should be combined with Alzheimer’s drugs for treatment in the future,” Chongzhao says.
The Martinos-based team reported a study validating the probe in a paper published last month in the journal Proceedings of the National Academy of Sciences. The researchers are now working to develop probes with increased sensitivity and longer wavelengths, with the goal of monitoring the changes in ROS concentrations under various treatments with Alzheimer’s drugs in preclinical studies.
They are also looking at the possibility of using the probes directly in humans, taking advantage of ocular imaging and the transparency of the eyes. They have already obtained preliminary data supporting this feasibility.