Simulations and experiments show how infrared laser irradiation could destroy the harmful protein clumps and tangles that indicate Alzheimer’s.
Alzheimer’s is one of the leading causes of death in America, and despite decades of research, there are still no drugs to slow or reverse the cognitive damage it causes. While drug developers try to crack the code of chemical interventions, scientists at the Tokyo University of Science and the Centre National de la Recherche Scientifique are focused on a non-pharmaceutical approach that involves breaking up amyloid protein clumps with infrared lasers.
A key biomarker of neurodegenerative diseases, including Alzheimer’s and Parkinson’s, is the formation of harmful plaques that contain aggregates, or fibrils, of a protein called beta-amyloid. In a study published in Journal of Physical Chemistry B, lead author Dr. Takayasu Kawasaki and colleagues shared the results of laser experiments and simulations, including new data about the morphology and structural evolution of amyloid fibrils after they’ve been zapped — with extreme precision — by lasers.
Kawasaki and colleagues used part of a yeast protein that can form its own amyloid fibrils as a target. In a series of laser experiments, they tuned the frequency of an infrared laser beam to that of the precise amide I band infrared spectrum of the fibril. Hitting it with just the right frequency causes the fibril to resonate until it breaks apart, dissipating the clumps of amyloid proteins that are so damaging to the brain.
They then used a series of spectroscopy techniques — measuring the spectra produced when matter interacts with electromagnetic radiation — to understand the details of the fibril’s structure and the process of its breaking apart.
The team was able to observe that the process started at the core of the fibril and spread outwards to its extremities. They saw the resonance created by tuning the laser to just the right frequency affected the fibril’s intermolecular hydrogen bonds. In this way, it separated and unclumped the proteins.
According to Kawasaki the results were an encouraging step toward a possible non-drug intervention, though he noted some limitations in a news release. For example, he said, “These experiments have limited spatial and temporal resolutions, thus preventing a full understanding of the underlying molecular mechanisms.”
“In view of the inability of existing drugs to slow or reverse the cognitive impairment in Alzheimer’s disease, developing non-pharmaceutical approaches is very desirable,” he said. “The ability to use infrared lasers to dissociate amyloid fibrils opens up a promising approach,” and more research is needed.
Meanwhile, other scientists are experimenting with different non-chemical approaches that can break up these fibrils and halt the progression of Alzheimer’s, including ultrasound.