Research identified a connection between a chronic infection in the gut caused by a common virus, cytomegalovirus (HCMV), and the development of Alzheimer’s disease in a subset of individuals. These findings were recently published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
How the research found the link
“We first discovered that immune cells in the brain, called microglia, turned on the expression of a specific gene, known as CD83, in a subset of people with Alzheimer’s disease,” explains Ben Readhead, MBBS, co-first author of the study and research associate professor with the ASU-Banner Neurodegenerative Disease Research Center in the Biodesign Institute at ASU. “As we worked to explain the presence of the immune cells, our first breakthrough came when we wondered whether these cells might indicate some kind of microbial exposure. On somewhat of a hunch, we looked at intestinal tissue from these same subjects and found an association with an unusual type of antibody. We were able to profile this antibody in spinal fluid samples and discovered it was actually an antibody against HCMV.”
HCMV is a common herpes virus with about 80% of individuals showing antibodies by the age of 80. Most of the time, people likely won’t even know they’ve contracted the disease or may have mild flu-like symptoms. However, this study showed that some people exposed to HCMV developed a chronic infection in the intestine. The virus then appears to have traveled to the brain where it may have contributed to the biological changes involved in the development of Alzheimer’s disease.
“When we looked at exposure to the virus in human brain cell models, we saw the increase of amyloid and phosphorylated tau proteins, which are the hallmark of Alzheimer’s disease,” says Dr. Readhead. “Based on those findings, and the unique constellation of the virus, antibodies and immune cells in the brain, we believe we’ve found a biologically unique subtype of Alzheimer’s disease. We estimate this subtype may affect 25 to 45% of people with the disease, although we need to see how these numbers bear out in additional patient populations.”
How brain and body donation supported this study
Thanks to Arizona’s unique biorepositories, specifically the Banner Sun Health Research Institute’s Brain & Body Donation Program, the researchers had access to tissues and samples from multiple areas of the body including the colon, vagus nerve, brain and spinal fluid.
“Having access to different tissues from the same individual including the colon was crucial to our study,” explains Dr. Readhead. “It led us to be able to track the immune response we were seeing in the brain to the various areas of the body and piece together this story that is consistent with chronic gut infection acting as a risk factor for eventual passage into the brain, potentially via the vagus nerve.”
Not only are these findings significant for the purposes of this study for Alzheimer’s disease, they could also play an important role in a wide variety of research going forward.
“At the moment, I’d consider the results from this study as interesting scientific findings, but we’re not sure what it means clinically just yet,” shares Dr. Readhead. “With continued research, potentially including clinical trials, we’re planning to tease out what the clinical relevance may be. It may be that the cross-tissue aspects of the story hold lessons for understanding peripheral impacts in other brain diseases as well.”
The next phase of this research
Researchers are working to apply the results of this study and dig further into this specific subtype of Alzheimer’s disease by identifying a blood-based biomarker for the HCMV infection.
“Initial efforts to develop a blood-based biomarker have been encouraging, showing 80% accuracy,” says Dr. Readhead. “Our goal is to be able to identify this particular type of HCMV infection through a blood test, then run a clinical trial to evaluate whether some kind of antimicrobial treatment, such as existing antiviral medications, might help treat or prevent this specific subtype of Alzheimer’s disease.”
If you’re interested in contributing to Alzheimer’s research, you can find a wide range of active studies on the Alzheimer’s Prevention Registry. Looking for more information on how brain and body donation programs work and how to participate? Check out this article.
