Solving Alzheimer's disease mysteries by applying laws of physics to biology

Some might say that Michael Gramlich’s groundbreaking research on Alzheimer's disease and dementia is huge, but in fact, you might call it small — that is, “molecular-level” small.  

“Thinking occurs across every scale, from the individual atom up to the entire brain,” he said. “Labs like mine start with how individual molecules interact, then combine their behavior in increasingly complex models at larger time and space scales to build understanding.”  

Associate Professor Michael Gramlich is an expert in biological physics, the study of how the physics of biological processes differs from standard laws of physics.

Professor Miranda Reed's research focuses on identifying drug interventions to target molecular processes that lead to brain degeneration and memory loss.

Gramlich and Reed work with students from both physics and pharmacy who are interested in the molecular processes surrounding memory.

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Gramlich, an associate professor in the College of Sciences and Mathematics’ Department of Physics, is an expert in biological physics, which means he studies how the physics of biological processes differs from standard laws of physics.  

“Biological physics is what drives the new creative models we’re trying to develop,” he said. “We discover new ways to understand the stuff we already know, but from a different perspective.” 

A major biological process he’s currently targeting is brain degeneration associated with the development of Alzheimer’s disease and related dementias. Gramlich conducts research out of two locations: one space in the Leach Science Center focused on fundamental physics and another at the Harrison College of Pharmacy, where he conducts research with Professor Miranda Reed on how drug interactions affect memory at the molecular level.  

The physics of memory maintenance   

One of Gramlich’s recent fundamental findings is a new model of how memory maintenance occurs at the molecular level, a necessity for the long-term recollection of memories. His model predicts how memory maintenance works not just in creating and recalling memories, but also in forgetting them — the telltale sign of Alzheimer’s disease and dementia. Gramlich said researchers have plenty of biological evidence for how these diseases progress, but no coherent model to understand or predict how the complex molecular processes lead to degeneration over time. 

“We knew that a breakdown in spontaneous communication between neurons of the brain correlates with a breakdown in actual memories,” he said. “But up until now, nobody really had a theoretical model to predict how breakdown in spontaneous communication leads to neurodegeneration in dementias like Alzheimer’s disease.”  

Gramlich’s next goal is to delve into the physics behind why Alzheimer’s disease and dementia patients not only struggle to recall memories but also have difficulty making new ones.  

“When you’re trying to make memories, it’s the same spontaneous communication process that’s thought to be involved, but nobody really knows how,” he said. 

Creative collaboration 

While Gramlich is uncovering how the process of memory works, Reed is finding the drug interventions that can impact that process. In their collaborative work, Gramlich pinpoints the brain’s many molecular processes and identifies which ones can lead to neurodegenerative disease. Reed and Gramlich then work together to find drug interventions that target these processes while minimizing disruption to other essential molecular processes.  

“I can come up with theories about neurological pathways and experiments to test all day long, but Dr. Reed is able to target these pathways with different drugs,” he said. “Working with her has been one of the best collaborations I’ve ever had.” 

So, what’s next for Gramlich, Reed and the field of Alzheimer’s and dementia research?  

“In the next 10 years, we are going to figure out how early dementia actually starts in the brain,” he said. “The research is indicating that for some types of dementia, it’s genetic, and by that, I mean it’s already starting when you’re born.” 

While he foresees an incredible amount of progress in the near future, Gramlich said scientists across the field need support to continue their groundbreaking work.  

“Science is the final frontier because it’s an endless frontier; there are always new things to figure out, and we are making significant progress,” he said. “We’ve got a vast amount of potential, but the one thing that would really help us accelerate this progress is resources.”