Scientists have observed in real time and reversed a chemical process linked to protein clumping associated with Alzheimer’s disease.
Using a molecule-measuring technique in laboratory tests, researchers tracked how certain metals can promote the clumping of amyloid-beta proteins.
In people with Alzheimer’s disease, these protein build-ups block neural pathways and prevent brain cells from communicating properly.
They also examined molecules known as chelators, which bind tightly to metal ions, and observed how they can disrupt or reverse the clumping process.
The work was led by Marilyn Rampersad Mackiewicz, associate professor of chemistry at Oregon State University.
The brain needs certain metals to function properly, but problems can arise when these metals are present in unbalanced quantities.
Mackiewicz said: “Too many of some metal ions, like copper, can interact with amyloid-beta proteins in ways that lead to protein aggregation, but most experiments have only shown the end result, not the interactions and aggregation process itself.
“We developed a method that lets us observe those interactions live, second by second, and directly measure how different molecules interrupt or reverse them.
“It shifts the question from ‘does something work?’ to ‘how does it work, and when?'”
One chelator in the study was shown, using a technique called fluorescence anisotropy, to capture metal ions effectively but in a non-selective way, meaning it did not distinguish between metals that promote clumping and those that do not.
The second chelator showed a strong ability to selectively target copper ions believed to play a role in Alzheimer’s disease.
Mackiewicz said: “That kind of real-time insight into how the protein aggregations form and unform is important for designing better treatments and for understanding why some widely used chemical approaches may not behave the way we assume they do. Alzheimer’s affects millions of families and while clinical treatments based on this work remain years away, discoveries like this can offer genuine hope, with the correct targeting, some of the brain damage might be reversible.”
Testing in more complex biological systems, including cellular and preclinical models, is expected to be the next step.
Mackiewicz said: “Many potential Alzheimer’s treatments fail due to an incomplete understanding of how amyloid-beta protein aggregation occurs.
“By directly observing and quantifying these interactions, our work provides a roadmap for creating more effective therapies.”
