Scientists at Oregon State University have teamed up with a group of undergraduate students to uncover new real-time details about a chemical process associated with Alzheimer’s disease. This discovery could help researchers design more effective drugs in the future.
Using specialized measurement techniques, the research team tracked how certain metals cause protein aggregation that contributes to the blockage of communication pathways in the brain, a key feature of Alzheimer’s disease.
The study was led by Marilyn Rampersad Makiewicz, an associate professor of chemistry in the OSU College of Science. Her team also observed how molecules called chelators can interfere with or reverse this harmful aggregation process. The survey results are ACS Omega.
Alzheimer’s disease and protein aggregation
Alzheimer’s disease is the most common type of dementia and is a long-term condition that affects memory and thinking ability for millions of older adults. It ranks as the sixth leading cause of death for people 65 and older, according to the Centers for Disease Control and Prevention.
In Alzheimer’s patients, amyloid beta protein accumulates and forms clusters that interfere with communication between brain cells. Metals are essential for the normal functioning of the brain, but problems can occur when their levels become unbalanced.
“Too much of some metal ions, such as copper, can interact with the amyloid beta protein in a way that causes protein aggregation, but most experiments only show the end result and not the interaction or aggregation process itself,” Professor Mackiewicz said. “We have developed a method that allows us to observe these interactions live every second and directly measure how different molecules disrupt or reverse them. This changes the question from ‘Does something work?’ “How and when does it work?”
Observing the chemistry of Alzheimer’s disease in real time
Chelating agents, whose name comes from the Greek word for nail, are a type of molecule that binds strongly to metal ions.
In this study, one chelating agent was able to effectively capture metal ions, but it did so without distinguishing between the different types. In other words, they were not specifically targeting the metals that cause amyloid-beta aggregation.
However, the second chelator showed a strong ability to selectively bind copper ions, which are thought to play an important role in the aggregation of Alzheimer’s disease-related proteins.
Toward more targeted Alzheimer’s disease treatment
“Such real-time insights into how protein aggregates form and fail to form are important for designing better treatments and understanding why some widely used chemical approaches don’t work as we expect,” Makiewicz said. “While Alzheimer’s disease affects millions of families, and clinical treatments based on this research are still years away, discoveries like this could offer real hope. With the right targets, some brain damage may be reversed.”
The project also focuses on the contributions of undergraduate researchers. With support from the SURE Science Program and donors Julie and William Reiersgaard, OSU student Alyssa Schroeder and Portland State University students Eleanor Adams, Dane Frost, Erica Lopez, and Jennie Giacomini were able to participate in the study.
Looking ahead, Makiewicz said next steps include testing these findings in more complex biological systems, such as cellular and preclinical models.
“Many potential Alzheimer’s disease treatments have failed because our understanding of how amyloid beta protein aggregation occurs is incomplete,” she says. “By directly observing and quantifying these interactions, our study provides a roadmap for creating more effective treatments.”
