A fascinating new collaborative study, between researchers at the University of Oxford and Tufts University, has found two common viruses may be working in tandem to trigger the earliest stages of Alzheimer’s disease. The findings build on a growing body of evidence implicating the herpes virus in neurodegenerative disease.
For over half a century the idea that microbial infections are a trigger for neurodegenerative disease has been floating on the sidelines of neuroscience. In the 1980s a number of studies pointed to associations between the onset of Alzheimer's disease and herpes simplex viral infections, but exactly how this very common virus could be influencing neurodegeneration was not clear.
A key 2020 study from a Tufts University team demonstrated exactly how a herpes infection could induce several pathological features of Alzheimer’s. The study used a new kind of 3D bioengineered brain model that populated a sponge-like structure with neural stem cells that could be coaxed into a variety of brain cells.
This type of brain tissue model was incredibly novel, and the findings were the first to explicitly show how the common viral infection can lead to pathological signs of Alzheimer’s. But a big question hovered over the findings. Considering more than two-thirds of the world’s population carry herpes simplex virus type I (HSV-1), there must be other factors that reactivate the dormant virus and trigger this cascade of events that lead to Alzheimer’s.
This new study looked to another common virus that has been associated with Alzheimer’s disease – varicella zoster virus (VZV). This virus causes chicken pox and, in later life, shingles. So using the 3D bioengineered brain model the researchers looked at whether VZV infection influences brain cells already seeded with dormant herpesvirus.
Interestingly, the research found exposing brain cells harboring dormant HSV-1 to VZV led to a reactivation of the herpesvirus and a cascade of the toxic plaques known to be signs of Alzheimer’s. However, all of these Alzheimer’s signs did not appear when brain cells were exposed to VZV in the absence of herpesvirus.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” said Dana Cairns, a researcher working on the project.
While the study does confidently propose this two-pronged viral mechanism can lead to Alzheimer’s disease, it does make clear this is likely only one pathway among many. And if reactivating dormant HSV-1 can trigger the progression of Alzheimer’s disease, there are probably a number of ways this can occur beyond an exposure to VZV.
“It’s still possible that other infections and other pathways of cause and effect could lead to Alzheimer’s disease, and risk factors such as head trauma, obesity, or alcohol consumption suggest they may intersect at the re-emergence of HSV in the brain,” added Cairns.
The study also speculates potential future Alzheimer’s problems may arise from the COVID-19 pandemic as SARS-CoV-2 infections have been known to reactivate dormant VSV and HSV-1 infections. It has been suggested the pandemic could increase future rates of neurodegenerative disease and the researchers behind this new study urge clinicians to keep a watchful eye on elderly patients over the coming years.
The new study was published in the Journal of Alzheimer’s Disease.
Source: Tufts University
