Researchers have recognized a link between persistent cytomegalovirus infections within the intestine and Alzheimer’s illness in sure people.
The virus could activate an immune response within the mind that contributes to Alzheimer’s pathology, together with the manufacturing of amyloid and tau proteins.
Chronic Gut Infection’s Link to Alzheimer’s
Researchers from Arizona State University and Banner Alzheimer’s Institute, together with their collaborators, have uncovered a potential link between a persistent intestine an infection attributable to a frequent virus and the event of Alzheimer’s illness in sure people.
The virus, often known as cytomegalovirus (HCMV), is a part of the herpes virus household and is often contracted in formative years by publicity to bodily fluids when the virus is energetic. While most individuals are uncovered to HCMV, it usually stays dormant and isn’t categorized as a sexually transmitted an infection.
However, the brand new analysis means that in some people, HCMV could keep energetic within the intestine and journey to the mind by the vagus nerve, a important communication pathway connecting the intestine and mind. Once within the mind, the virus could disrupt the immune system and set off adjustments linked to Alzheimer’s illness.
Potential Treatment and Diagnosis Advances
If the researchers’ hypotheses are confirmed, they are able to consider whether or not current antiviral medicine may deal with or stop this type of Alzheimer’s illness. They are presently growing a blood check to establish individuals who have an energetic HCMV an infection and who may profit from antiviral treatment.
“We think we found a biologically unique subtype of Alzheimer’s that may affect 25% to 45% of people with this disease,” mentioned Dr. Ben Readhead, co-first creator of the examine and analysis affiliate professor with ASU-Banner Neurodegenerative Disease Research Center within the Biodesign Institute at ASU. “This subtype of Alzheimer’s includes the hallmark amyloid plaques and tau tangles—microscopic brain abnormalities used for diagnosis—and features a distinct biological profile of virus, antibodies and immune cells in the brain.”
The findings had been printed right this moment in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. Researchers from ASU, Banner Alzheimer’s Institute, Banner Sun Health Research Institute, and the Translational Genomics Research Institute (TGen) led the collaborative effort, which included investigators with UMass Chan Medical School, Institute for Systems Biology, Rush University Medical Center, Icahn School of Medicine at Mount Sinai, and different establishments.
The analysis group means that some individuals uncovered to HCMV develop a persistent intestinal an infection. The virus then enters the bloodstream or travels by the vagus nerve to the mind. There, it’s acknowledged by the mind’s immune cells, known as microglia, which activate the expression of a particular gene known as CD83. The virus could contribute to the organic adjustments concerned within the improvement of Alzheimer’s.
The Role of Microglia in Alzheimer’s Development
Microglia, or the mind’s immune cells, are activated when responding to infections. While initially protecting, a sustained enhance in microglial exercise could result in persistent irritation and neuronal harm, which is implicated within the development of neurodegenerative ailments, together with Alzheimer’s.
In a examine printed earlier this 12 months in Nature Communications, the researchers discovered that the postmortem brains of analysis members with Alzheimer’s illness had been extra probably than these with out Alzheimer’s to harbor particularly CD83(+) microglia. While exploring why this occurred, they found an antibody within the intestines of those topics — per the likelihood that an an infection may contribute to this type of Alzheimer’s.
In the latest examine, investigators sought to grasp what could be driving the intestinal antibody manufacturing. The group examined spinal fluid from these similar people, which revealed that the antibodies had been particularly in opposition to HCMV. This prompted a seek for proof of HCMV an infection within the gut and mind tissue of those topics – which they discovered.
They additionally noticed HCMV inside the vagus nerve of the identical topics, elevating the likelihood that that is how the virus travels to the mind. Working with RUSH University, the researchers had been capable of reproduce the affiliation between cytomegalovirus an infection and CD83(+) microglia in an unbiased cohort of Alzheimer’s sufferers.
To additional examine the affect of this virus, the analysis group then used human mind cell fashions to display the virus’s means to induce molecular adjustments associated to this particular type of Alzheimer’s illness. Exposure to the virus did enhance the manufacturing of amyloid and phosphorylated tau proteins and contributed to the degeneration and demise of neurons.
Implications for Alzheimer’s Research and Treatment
HCMV can infect people of all ages. In most healthy people, an infection happens with out signs however could present as a delicate, flu-like sickness. About 80% of individuals present proof of antibodies by age 80. Nonetheless, the researchers detected intestinal HCMV solely in a subset of people, and this an infection appears to be a related issue within the presence of the virus within the mind. For this motive, the researchers be aware that merely coming into contact with HCMV, which occurs to virtually everybody, shouldn’t be trigger for concern.
And, though researchers proposed greater than 100 years in the past that dangerous viruses or microbes may contribute to Alzheimer’s illness, no single pathogen has constantly been linked to the illness.
The researchers suggest these two research illustrate the potential affect that infections can have on mind health and neurodegeneration broadly. Yet, they add that unbiased research are wanted to place their findings and ensuing hypotheses to the check.
The NOMIS Foundation, Banner Alzheimer’s Foundation, National Institutes of Health, and Arizona Alzheimer’s Consortium supported the examine. Arizona’s distinctive biorepositories, significantly the Brain and Body Donation Program at Banner Sun Health Research Institute, supplied tissue samples and sources, together with the colon, vagus nerve, mind, and spinal fluid. Rush University-led Religious Orders Study and Memory and Aging Study supplied extra mind samples and knowledge. This allowed researchers to conduct a extra nuanced investigation, highlighting the systemic quite than purely neurological roots of Alzheimer’s illness.
“It was critically important for us to have access to different tissues from the same individuals. That allowed us to piece the research together. Arizona is the only place I know of where a study like this could have been done, and we’re grateful to the Banner Health Brain and Body Donation Program for its support,” mentioned Readhead, additionally the Edson Endowed Professor of Dementia Research on the middle.
“We are extremely grateful to our research participants, colleagues, and supporters for the chance to advance this research in a way that none of us could have done on our own,” mentioned Dr. Eric Reiman, Executive Director of Banner Alzheimer’s Institute and the examine’s senior creator. “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.”
The findings of the current examine increase an essential query: Could antiviral drugs assist deal with Alzheimer’s sufferers who’ve a persistent HCMV an infection?
The investigators are working now on a blood check to establish people with any such persistent intestinal HCMV an infection. They hope to make use of it together with rising Alzheimer’s blood exams to judge whether or not current antiviral medicine might be used to deal with or stop this type of Alzheimer’s illness.
Reference: “Alzheimer’s disease-associated CD83(+)microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain” 19 December 2024, Alzheimer’s & Dementia.
DOI: 10.1002/alz.14401
Research establishments concerned within the examine, printed within the journal Alzheimer’s & Dementia: ASU-Banner Neurodegenerative Disease Research Center within the Biodesign Institute at ASU; Weill Cornell Medicine; Icahn School of Medicine; University of Massachusetts Chan Medical School; The Translational Genomics Research Institute; Institute for Systems Biology; Serimmune, Inc; Rush University Medical Center; Banner Sun Health Research Institute; and Banner Alzheimer’s Institute.