Researchers from Arizona State University (ASU) and Banner Alzheimer's Institute, working with top institutions, have discovered a possible link between a cytomegalovirus (HCMV)-caused chronic gut infection and Alzheimer's disease. This groundbreaking study suggests that this virus may influence a unique form of Alzheimer's disease in a subset of patients—an estimated 25% to 45%. HCMV, part of the herpes virus family, is highly prevalent, with most people exposed to it in early life. The virus is typically asymptomatic or causes mild flu-like symptoms, but it can persist in the body in an active state, especially in the gut.

Researchers hypothesise that in certain individuals, the virus travels from the gut to the brain via the vagus nerve, a crucial pathway linking these two organs. Once in the brain, HCMV appears to influence immune responses and contribute to hallmark Alzheimer’s characteristics, such as amyloid plaques and tau tangles.

Dr. Ben Readhead, co-first author and research associate professor at ASU’s Biodesign Institute, explained, “We think we found a biologically unique subtype of Alzheimer’s that may affect 25% to 45% of people with this disease.”

The study highlights the role of microglia, the brain’s immune cells, in responding to infections. Persistent activation of microglia due to HCMV could lead to chronic inflammation and neuronal damage, key factors in Alzheimer’s progression. Researchers identified specific antibodies in the intestines and spinal fluid of Alzheimer’s patients, suggesting a link between intestinal infections and brain changes.

“It was critically important for us to have access to different tissues from the same individuals,” noted Readhead, adding that Arizona’s unique biorepositories were instrumental in advancing the research.

Published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study demonstrates how HCMV may drive the biological changes underlying a distinct Alzheimer’s subtype.

Working with partners like Rush University Medical Centre, researchers observed that HCMV infection increased production of amyloid and tau proteins, contributing to neurone degeneration and death. The research team is now developing a blood test to identify individuals with active HCMV infections.

This test could pave the way for antiviral treatments to prevent or manage this specific form of the disease, in conjunction with emerging Alzheimer's diagnostics. “We’re excited about the chance to have researchers test our findings in ways that make a difference in the study, subtyping, treatment, and prevention of Alzheimer’s disease,” said Dr. Eric Reiman, Executive Director of Banner Alzheimer’s Institute.

If confirmed through independent studies, the findings could revolutionize Alzheimer’s treatments.  Researchers propose evaluating existing antiviral drugs for their potential to halt or slow the progression of HCMV-related Alzheimer’s.

“The possibility that antiviral medications could help patients with this chronic infection is an exciting avenue to explore,” said Readhead. The study involved contributions from multiple institutions, including ASU-Banner Neurodegenerative Disease Research Centre, Translational Genomics Research Institute, Rush University Medical Centre, and the National Institutes of Health, among others. Funding came from the NOMIS Foundation, the Banner Alzheimer’s Foundation, and the Arizona Alzheimer’s Consortium.

The researchers emphasize that, while nearly everyone is exposed to HCMV, only a subset develops this intestinal infection linked to Alzheimer's.  Their findings underscore the importance of systemic health in understanding neurodegenerative diseases and offer hope for innovative treatments that could improve the lives of millions.