For years, the idea that infections could play a role in Alzheimer's disease was met with skepticism. But Benjamin Readhead, a research associate professor at the ASU-Banner Neurodegenerative Disease Research Center, couldn't ignore the mounting evidence.
As he pored over data from brain donors and immune system profiles, an unexpected pattern began to emerge— one that pointed to a common virus lurking in the background: human cytomegalovirus.
Readhead, discussing his recent study, emphasized the growing interest in understanding how infections might contribute to neurodegenerative diseases.
"What I'm really laser focused on at the moment is trying to understand the interactions between different sorts of infections – often with common viruses or bacteria – and interactions that that has with the immune system and other biological pathways, and the ways that that impacts or potentially contributes to diseases like Alzheimer's disease," Readhead said.
Eric Reiman, CEO of Banner Alzheimer's Institute, also noted the importance of exploring infectious agents in Alzheimer's. He said for many years, the suggestion of an infectious contribution to Alzheimer's disease seemed improbable.
The study builds upon previous findings that certain immune cells may play a role in Alzheimer's pathology.
"One of the things that grabbed our attention was there was a certain immune cell type that we were seeing in the brain tissue of some people with Alzheimer's disease but not in everyone," Readhead said. "It was maybe one-third to one-fourth of patients with Alzheimer's disease."
The study used advanced immunohistochemistry and genetic profiling. Immunohistochemistry is a technique that uses antibodies to identify the presence of diseases. The researchers identified a strong correlation between nervous system cells and human cytomegalovirus.
"We're able to apply this cutting-edge technology to the spinal fluid samples, which was able to tell us what viruses, what bacteria are these antibodies seeing ... And that's where we got to cytomegalovirus," Readhead said.
This innovative approach could help identify those at risk for Alzheimer's before symptoms manifest, providing an opportunity for earlier intervention. According to Reiman, a related study looked at the cells of unimpaired brain donors to find pathological evidence of Alzheimer's disease before it was diagnosed.
Qi Wang is a research assistant professor at the ASU-Banner Neurodegenerative Disease Research Center. Wang contributed to the computational side of the research and observed a link between a genetic marker and the complex tissue interactions that may influence Alzheimer's disease.
"We noticed that for this small subset of this microglia, we were able to identify a particular genetic or maybe gene marker called CD83," said Wang.
The presence of both cytomegalovirus and a consistent genetic marker in brain tissue, transverse colon and vagal nerve suggests a complex, cross-tissue interaction between viral infections and the adaptive immune response in Alzheimer's patients. These findings were replicated in an independent cohort, further strengthening the potential association.
To test the direct impact of human cytomegalovirus in Alzheimer's disease behavior, the researchers conducted experiments using cerebral organoids — lab-grown, miniature brain models.
"We were able to grow brain organoids, which are these microscopic brain-in-a-dish systems that contain the complexity of different cells that are present in the brain and then infect them with CMV (cytomegalovirus)," Readhead said.
These findings suggest that human cytomegalovirus infection could accelerate the development of Alzheimer's-related neurodegeneration, potentially opening new avenues for targeted interventions.
Reiman said there may be promise of a breakthrough in prevention therapies. For example, one potential avenue is the exploration of antiviral therapies for Alzheimer's patients with biomarker evidence of human cytomegalovirus and certain genetic markers.
"We're really excited about that prospect — or at least testing that prospect — because at the moment we don't know, but we think it will be worth it ... Is it helpful? And if so, who is it most helpful to?" Readhead said.
Wang also discussed the role of artificial intelligence in advancing the research.
"We are looking into how to use next generation computational methods including artificial intelligence, deep learning, machine learning," Wang said. "Better understand all these molecular profiles, but that will depend on a lot of data, lots of computing resources."
Reiman also shared encouraging words for those interested in Alzheimer's and biomedical research.
"I would not be daunted by the recent attacks on science right now," Reiman said. "It is extremely important to interest the best and brightest people, to participate in the scientific and clinical fight against these devastating diseases and to advance their research in a number of important ways. It is a time of unprecedented promise, scientifically."
Edited by Sophia Ramirez, Sophia Braccio and Katrina Michalak.
Reach the reporter at ammaarzindani@asu.edu.
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