summary: Researchers have linked chronic intestinal infections caused by cytomegalovirus (HCMV) to a unique subtype of Alzheimer’s disease. The virus travels from the gut to the brain via the vagus nerve, altering the immune response and potentially causing hallmark changes of Alzheimer’s disease, such as amyloid plaques and tau tangles.
Although HCMV infection is common and usually harmless, this study found that it can cause chronic brain inflammation in certain people. Researchers demonstrated how HCMV induces molecular changes associated with Alzheimer’s disease in a human brain cell model.
These findings highlight the potential for antiviral therapy to address this subtype of Alzheimer’s disease. Ongoing research aims to develop a blood test to identify patients with chronic HCMV infection and evaluate treatment options.
Important facts:
- Gut-brain link: HCMV infection in the intestine can reach the brain via the vagus nerve and cause Alzheimer’s disease.
- Molecular influence: The virus causes the production of amyloid and tau, which causes neuronal damage.
- Treatment possibilities: Researchers are investigating antiviral drugs to treat this subtype of Alzheimer’s disease.
sauce: arizona state university
Researchers at Arizona State University and the Banner Alzheimer’s Disease Research Institute, along with their collaborators, have discovered a surprising link between chronic intestinal infections caused by a common virus and the development of Alzheimer’s disease in some people. I discovered a necessary relationship.
It is thought that most humans are exposed to this virus, called cytomegalovirus, or HCMV, during the first few decades of life. Although cytomegalovirus is one of nine herpesviruses, it is not considered a sexually transmitted disease. Viruses are usually transmitted through exposure to body fluids and can only spread when the virus is active.
In some people, the virus remains active in the gut and can reach the brain via the vagus nerve, a vital information highway between the gut and the brain, according to a new study. Once the virus gets there, it can alter the immune system and contribute to other changes associated with Alzheimer’s disease.
If the researchers’ hypothesis is confirmed, it could be possible to evaluate whether existing antiviral drugs can treat or prevent this form of Alzheimer’s disease. They are currently developing a blood test to identify people with active HCMV infection who may benefit from antiviral drugs.
“We believe we have discovered a biologically unique subtype of Alzheimer’s disease that may affect 25% to 45% of people with Alzheimer’s disease,” said co-lead author of the study. , said Dr. Ben Readhead, ASU Banner Research Associate Professor in Neurodegenerative Disease Research. ASU’s Center for Biodesign Research Institute.
“This subtype of Alzheimer’s disease includes characteristic amyloid plaques and tau tangles (microscopic brain abnormalities used in diagnosis), and a distinct biology of viruses, antibodies, and immune cells in the brain. It is characterized by a scientific profile.
The findings were published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Researchers from ASU, the Banner Alzheimer’s Disease Institute, the Banner Sun Health Institute, and the Translational Genomics Institute (TGen) led the collaboration, including the University of Massachusetts Medical School, the Systems Biology Institute, and Rush University Medicine. Center, Icahn University researchers were also included. Mount Sinai Medical and Other Institutions.
The research team suggests that some people exposed to HCMV develop chronic intestinal infections. The virus then enters the bloodstream or travels to the brain through the vagus nerve.
There, they are recognized by immune cells in the brain called microglia, which turn on the expression of a specific gene called CD83. This virus may contribute to biological changes involved in the development of Alzheimer’s disease.
Role of immune cells in the brain
Microglia, or immune cells in the brain, are activated when responding to infections. Although initially protective, sustained increases in microglial activity can lead to chronic inflammation and neuronal damage, which are implicated in the progression of neurodegenerative diseases, including Alzheimer’s disease.
In a study published earlier this year innature communicationsResearchers found that the postmortem brains of study participants with Alzheimer’s disease were more likely to specifically harbor CD83(+) microglia than participants without Alzheimer’s disease.
While investigating why this happened, they found antibodies in the guts of these subjects. This is consistent with the possibility that infectious diseases contribute to this form of Alzheimer’s disease.
In the latest study, researchers sought to understand what drives intestinal antibody production. The researchers tested the spinal fluid of these same individuals and found that antibodies were present specifically for HCMV. This led to investigation and discovery of evidence of HCMV infection in the gut and brain tissue of these subjects.
They also observed the presence of HCMV within the vagus nerve of the same subjects, raising the possibility that this is how the virus travels to the brain. Researchers, in collaboration with RUSH University, were able to reproduce the association between cytomegalovirus infection and CD83(+) microglia in an independent cohort of Alzheimer’s disease patients.
To further investigate the effects of this virus, the research team used a human brain cell model to demonstrate the virus’ ability to induce molecular changes associated with this particular form of Alzheimer’s disease. Exposure to the virus increased the production of amyloid and phosphorylated tau proteins, contributing to neuronal degeneration and death.
Is HCMV the cause of Alzheimer’s disease in some people?
HCMV can infect people of all ages. Most healthy people have no symptoms when infected, but some may experience mild flu-like symptoms. About 80% of people show evidence of antibodies by age 80.
Nevertheless, researchers have detected enteric HCMV only in some individuals, and this infection appears to be a factor related to the presence of the virus in the brain. For this reason, researchers point out that simply being exposed to HCMV, which occurs in almost everyone, is not a cause for concern.
Additionally, although researchers proposed more than 100 years ago that harmful viruses and microorganisms could contribute to Alzheimer’s disease, no single pathogen has been consistently associated with Alzheimer’s disease. There is no.
The researchers propose that these two studies demonstrate the potential effects that infectious diseases can have on brain health and neurodegeneration broadly. However, they add that independent research is needed to test the findings and resulting hypotheses.
The NOMIS Foundation, the Banner Alzheimer’s Disease Foundation, the National Institutes of Health, and the Arizona Alzheimer’s Disease Consortium supported this research. Arizona’s unique biorepositories, specifically Banner Sun Health Institute’s Brain and Body Donation Program, provided tissue samples and resources including colon, vagus nerve, brain, and spinal fluid.
Additional brain samples and data were provided by the Rush University-led Religious Order Study and the Memory and Aging Study. This has allowed researchers to conduct more nuanced investigations, focusing on the systemic rather than purely neurological causes of Alzheimer’s disease.
“Having access to different tissues of the same individual was very important to us. This allowed us to bring the research together. It’s the only place I know of, and I’m grateful for the support of the Banner Health Brain and Body Donation Program,” said Readhead, who is also the Edson Endowed Professor in Dementia Research. center.
“We are extremely grateful to our study participants, colleagues, and supporters for giving us the opportunity to advance this research in ways that none of us could have done alone.” said Executive Director Dr. Eric Lyman. Senior author of the study.
“We are excited about the opportunity to have researchers test our findings in ways that will make a difference in Alzheimer’s disease research, subtypes, treatment, and prevention.”
Recent findings raise an important question: Can antiviral drugs help treat Alzheimer’s patients with chronic HCMV infection?
Researchers are currently working on a blood test to identify patients with this type of chronic intestinal HCMV infection. They hope to use it in conjunction with an emerging Alzheimer’s disease blood test to assess whether existing antiviral drugs can be used to treat or prevent this form of Alzheimer’s disease.
Research institutions that participated in the research published in the journal Alzheimer’s disease and dementia: ASU-Banner ASU Biodesign Institute Neurodegenerative Disease Research Center; Weill Cornell Medicine; Icahn School of Medicine; University of Massachusetts Chan School of Medicine. Translational Genomics Institute; Systems Biology Institute; Selimun Inc.; Rush University Medical Center; Banner SunHealth Institute; Banner Alzheimer’s Research Institute.
About this microbiome and Alzheimer’s disease research news
author: Sandy Keaton Leander
sauce: arizona state university
contact: Sandy Keaton Leander – Arizona State University
image: Image credited to Neuroscience News
Original research: Open access.
“Alzheimer’s disease-associated CD83(+) microglia are associated with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagus nerve, and brainWritten by Ben Readhead et al. Alzheimer’s disease and dementia
abstract
Alzheimer’s disease-associated CD83(+) microglia are associated with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagus nerve, and brain
introduction
There may be a microbial contribution to Alzheimer’s disease (AD), but the conclusions are inconclusive. We recently reported an AD-associated CD83(+) microglial subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).
method
We investigated this association using immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments.
result
CD83(+) microglia in the superior frontal gyrus (SFG) have elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in the cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagus nerve. related to. This association was also replicated in an independent AD cohort. Cerebral organoids infected with HCMV exhibited pathophysiological hallmarks of AD (Aβ42 and pTau-212) and accelerated neuronal cell death.
discussion
Findings indicate a complex tissue-to-tissue interaction between HCMV and CD83(+) microglia-related adaptive immune responses in AD patients. This may represent an opportunity for antiviral therapy in patients with Alzheimer’s disease and those with biomarker evidence of HCMV, IgG4, or CD83(+) microglia.
