With the development of a blood test to identify patients with chronic HCMV infection on the horizon, this research might not just explain why some people develop Alzheimer's - it might also point the way toward preventing it. In the end, the key to understanding this devastating brain disease may have been hiding in our gut all along.
The study employed a multi-pronged approach to investigation. Researchers analyzed tissue samples from multiple areas of the body (brain, gut, and vagus nerve) using immunohistochemistry to detect the presence of HCMV and IgG4. They also examined cerebrospinal fluid samples to look for specific antibodies against HCMV. Additionally, they used laboratory-grown brain organoids to study the direct effects of HCMV infection on brain cells. The study included samples from both Alzheimer's patients and healthy controls, with findings validated in an independent cohort.
The key findings showed that patients with CD83-positive microglia had significantly higher levels of both HCMV and IgG4 in multiple tissues. In the laboratory experiments, HCMV infection led to increased production of Alzheimer's-associated proteins and increased cell death. The study found strong statistical associations between these various factors, suggesting a connected pathway from viral infection to disease progression.
While the study shows strong associations, it cannot definitively prove that HCMV causes Alzheimer's disease. The sample sizes, while adequate, could be larger in future studies. Additionally, the study cannot explain why some people with HCMV infection develop Alzheimer's while others don't, suggesting other factors are likely involved.
The study suggests a potential new pathway in Alzheimer's disease development involving viral infection and immune response. This could lead to new therapeutic approaches, particularly in patients showing specific biomarkers. The findings also highlight the importance of considering multiple body systems in disease research, rather than focusing solely on the brain.
The research was supported by various organizations, including the National Institute on Aging, the NIH, the Global Lyme Alliance, and the Arizona Alzheimer's Consortium. The researchers disclosed several potential conflicts of interest: one author has served as a consultant for multiple pharmaceutical and therapeutic companies, including J&J, Diagenic, Pfizer, Cognito Therapeutics, and others. Additionally, four of the authors are listed as co-inventors on a patent application for an IgG4-based peripheral biomarker to detect CD83(+) microglia. The remaining authors declared no relevant conflicts of interest.
This research was published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association on December 19, 2024. The study is titled "Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain" (DOI: 10.1002/alz.14401). was an experimental study using human tissue samples.