Using a specialized measurement technique, the team tracked how certain metals can trigger the clumping of proteins that contributes to blocked communication pathways in the brain, a key feature of Alzheimer’s.

The study was led by Marilyn Rampersad Mackiewicz, an associate professor of chemistry in the OSU College of Science. Her team also observed how molecules called chelators can interfere with or even reverse this harmful clumping process. The findings were published in ACS Omega.

Alzheimer’s Disease and Protein Clumping

Alzheimer’s disease is the most common type of dementia, a long-term condition that affects memory and thinking abilities in millions of older adults. According to the Centers for Disease Control and Prevention, it ranks as the sixth-leading cause of death among people age 65 and older.

In people with Alzheimer’s, amyloid-beta proteins accumulate and form clusters that disrupt communication between brain cells. While metals are essential for normal brain function, problems can arise when their levels become unbalanced.

“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,” Mackiewicz said. “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?'”

Watching Alzheimer’s Chemistry in Real Time

A chelator, whose name comes from the Greek word for claw, is a type of molecule that binds tightly to metal ions.

In the study, one chelator was able to capture metal ions effectively, but it did so without distinguishing between different types. In other words, it did not specifically target the metals that drive amyloid-beta clumping.

A second chelator, however, showed a strong ability to selectively bind to copper ions, which are believed to play a key role in Alzheimer’s-related protein aggregation.

Toward More Targeted Alzheimer’s Treatments

“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,” Mackiewicz said. “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.”

The project also highlights the contributions of undergraduate researchers. Support from the SURE Science Program and donors Julie and William Reiersgaard enabled students Alyssa Schroeder of OSU and Eleanor Adams, Dane Frost, Erica Lopez and Jennie Giacomini of Portland State University to take part in the work.

Looking ahead, Mackiewicz said the next phase will involve testing these findings in more complex biological systems, including cellular and preclinical models.

“Many potential Alzheimer’s treatments fail due to an incomplete understanding of how amyloid-beta protein aggregation occurs,” she said. “By directly observing and quantifying these interactions, our work provides a roadmap for creating more effective therapies.”