Researchers at the Beckman Institute for Advanced Science and Technology will use a unique set of imaging technologies to study Alzheimer’s disease on a scale never seen before.
Jonathan Swedler, Carley Illinois College of Medicine Professor of Biomedical Sciences and Translation and Professor of Chemistry, and Van Lamm, CI MED Associate Professor of Biomedical Sciences and Translation and Professor of Bioengineering, will collaborate on a five-year project to integrate MRI and mass spectrometry imaging to capture a wide range of of images in an animal model of Alzheimer’s disease. Their research is supported by a $3 million grant from the National Institute on Aging of the National Institutes of Health.
One overall goal is to understand what happens at the molecular level in a mouse model of Alzheimer’s disease as a function of age and stage of the disease.
“Although there is a genetic predisposition to Alzheimer’s disease, not many people end up with it,” Swedler said. And many people who do not have a genetic predisposition end up with Alzheimer’s disease. There is growing evidence that signatures at the molecular level may indicate that someone will develop Alzheimer’s disease, decades before anything appears functional.”
While Alzheimer’s disease has been studied extensively, the complexities of its causes and genetic influence remain unknown. For this reason, researchers are looking for factors they may have missed. They want to know what differs chemically between a normal aging brain and an aging brain heading toward Alzheimer’s disease.
“There is some evidence that certain groups of neurons are particularly vulnerable, and we want to know why,” Swedler said. “Knowing that a certain group of neurons is dying is one thing, but if we can understand what’s changing chemically, others can design an intervention to prevent that.”
To obtain expanded chemical information on a mouse model of the brain with Alzheimer’s disease, the duo will use a unique combination of MRI and MSI imaging techniques.
“With most shooting techniques, you have to know what you’re looking at,” Sweedler said. “You pick the molecule and say, ‘Where is it, how much is it there and what is its exact chemical form?'” Our approach is different because the combination of MRI and MSI does not have this requirement. We broadcast a wide net and say, ‘What’s in there?’ And we do it on a spatial scale that hasn’t been done before, from single-cell images to whole brains.”
Due to the extraction of tissue taken into the MSI, it is able to map hundreds or even thousands of molecules. This detailed chemical information allows researchers to reduce assumptions made about the disease, allowing them to proceed with an unbiased approach.
MRI is completely non-invasive and provides a whole-brain reference for reconstructing and revealing the unique spatial arrangements of molecules in different stages of Alzheimer’s disease.
The combination of the two technologies leads to the strengths of both imaging modalities.
“If we can build connections between the information provided by the MSI at the biochemical level and the macroscopic changes that can be observed on the MRI, we can provide a basis for a molecular level interpretation of the MRI,” said Lam. “You photograph a person, and then by seeing something, you can deduce what is going on underneath.”
The researchers, who were initially approached through Yuxuan graduate student Richard Xie, were encouraged in their collaboration by the Beckman Institute.
“We can always talk about big ideas, but we really need the bright students to act as a bridge between the different groups to bring things to fruition,” Lamm said.
Lamm and Swedler are also excited to collaborate with Orly Lazarov, professor of anatomy and cell biology at the University of Illinois College of Medicine at Chicago, who provides deep expertise in the molecular and cellular processes underlying cognition and cognitive dysfunction in Alzheimer’s disease.
“We look forward to working continuously alongside and with other Beckmann collaborators to drive this direction forward and pursue long-term research goals beyond the time limit of this grant,” said Lamm. “The scholarship will end, but our cooperation will continue.”
Editor’s Notes: The research reported in this news release was supported by the National Institute on Aging of the National Institutes of Health under award number R01AG078797. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The original version of this article can be found by Gina Kurtzweil of the Beckman Institute here.