It may not be the most mainstream theory, but there is a growing populus of scientists and doctors who put weight behind the thought process that the root of Alzheimer’s could lie with microbes. We explored this in early July here on the blog, but now we delve in a bit deeper. An intricate new study published in late June in Neuron revealed that certain viruses are not only most common in the brains of people with Alzheimer’s, but that they play a direct role in the chain of events responsible for the fatal neurodegenerative disorder.  

The study’s author, Joel Dudley, an associate professor of genetics and genomic sciences at Mount Sinai’s Ichan School of Medicine, shares that the findings were anything but expected. “We actually had no intentions of looking at this theory. We were actually looking for new drug targets,” he told Gizmodo in an interview. “But by taking this data-driven approach on an exciting new data set, we were led down this path of looking at viruses.” 

Dudley and his team studied brain samples taken from people diagnosed with Alzheimer’s posthumously and compared these to samples from people who had died without the disease. The data from the samples was amassed from three large brain banks by the National Institutes of Health, via their Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD) consortium. This element was of note  because it provided the team with access to the raw genomic sequences of the brains. Usually, in these types of studies, scientists only examine genes specifically known to be human, but the NIH data allowed them to sequence and identify genetic material belonging to viruses that had made their home in the brain. 

Based on that genetic footprint, the team found several species of herpes viruses that were more common in the brains of people with Alzheimer’s. Greater amounts of herpes virus found in the brain were also associated with someone having a worse level of dementia before their death, further suggesting a clear link. And of all the viruses they examined, there were two that showed the strongest connection to Alzheimer’s: human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7). 

 “That was just the beginning of the thread we started pulling on,” Dudley shared in his Gizmodo interview. “Just because we found greater abundance in the Alzheimer’s cases, that doesn’t rule out the possibility that these viruses could just be passengers.” 

With this information, Dudley’s team delved deeper. Using the data to create computer models of gene interactions in a person’s brain with any viral DNA and RNA they discovered that HHV-6A and HHV-7 genes were regularly turning on and off human genes in these brains, and vice-versa.  Also that the human genes that most interacted with HHV-6A and HHV-7 were also genes that have been previously implicated in raising someone’s risk of Alzheimer’s. These interactions were also found in areas of the brain especially affected by the disease, such as the hippocampus. 

“We could see that the viruses were potentially activating known Alzheimer’s genes and suppressing other genes [thought to be related to the disease],” Dudley said. “So these viruses could perhaps be the environmental factor that trigger someone’s genetic susceptibility to Alzheimer’s.” 

While the researchers had little interest in proving or disproving the so-called viral hypothesis of Alzheimer’s when they started, the results they discovered along the way led them to believe that the results are rather convincing in that area and behoove further exploration. It is of note that the study is welcome validation for some researchers who have doggedly argued for a viral origin. 

“My main reaction on seeing this article was pleasurable, as it adds a further study to the steadily increasing number of papers that support a microbial role in Alzheimer’s,” Ruth Itzhaki, a professor emeritus of molecular neurobiology at Britain’s University of Manchester who has argued for the hypothesis since at least 1991, told Gizmodo. “The numbers are particularly gratifying in view of the derision and vituperative hostility to the concepts that some of us endured for decades—with the consequent extreme problems in funding the work and in publishing the results.” 

Interestingly enough, most of the research into this viral hypothesis has focused on a different herpes virus, herpes simplex 1 (HSV-1), known most commonly as the culprit behind cold sores. In Itzhaki’s research, of more than 130 studies that have found indirect evidence of a viral link, only a few have singled out HHV. 

Dudley’s team did find an link between HSV-1 and Alzheimer’s, it just wasn’t to the same grade as HHV-6A and HH7.  He doesn’t suppose the results discount the possibility that HSV-1 could be involved. But because HSV-1 is relatively easier to detect through blood tests, he suggests that researchers relying on older methods could have simply missed the stronger link between Alzheimer’s and HHV. 

At an early age, people are usually infected with HHV-6A and HHV-7. For children, it materializes as the mild skin disorder roseola. But the strains have been theorized to cause other neurological disorders. In particular, HHV-6 has been linked to multiple sclerosis, the autoimmune disorder that progressively deteriorates the central nervous system. 

These viruses are quite widespread,  HHVs are found in about 90 percent of Americans, and HSV-1 is found in roughly 50%.  It’s important to recognize that not everyone develops Alzheimer’s. However, it’s impossible not to make the connection that viral infections, albeit small, could be a key piece to the cause of Alzheimer’s.   

From what we’ve learned about these viruses, it’s believed that they  lie dormant somewhere in the body, and then they travel to and stealthily infect the brain and / or nervous system at some point in our lives. It’s believed that something reactivates these viruses, whether it be an illness or stress, that further weakens the immune system. At that point, there must be something else that makes people’s brains interact with the viruses in a way that hastens Alzheimer’s. 

According to the study, Dudley’s research revealed that both viruses interacted with the human genes responsible for producing beta-amyloid, the protein that forms the  plaques that destroy the brains in Alzheimer’s patients. This finding supports the other theory that our natural immunity system can actually cause the disease. This theory, that both Dudley and Itzhaki support, indicates that beta-amyloid is used by our brain to defend itself against infection. In people who end up having Alzheimer’s, this defense mechanism has clearly gone wrong. 

If this is the case, Dudley believes that there might be more than one species of virus or even bacteria capable of setting off Alzheimer’s and other neurological conditions. This overarching theory brings to mind that there is much more to learn about the viral / bacteria and Alzheimer’s connection. But progress is being made, and the more we discover, the more researchers and scientists are able to develop and test drugs that might giver Alzheimer’s sufferers a fighting chance.  

Sources: 

https://www.cell.com/neuron/fulltext/S0896-6273(18)30421-5?code=cell-site 

https://www.ncbi.nlm.nih.gov/pubmed/25462444 

https://www.cdc.gov/nchs/products/databriefs/db304.htm 

Alzheimer’s
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