In 2022, a fascinating collaborative study by researchers at the University of Oxford and Tufts University showed that two common viruses may work together to induce the early stages of Alzheimer's disease. The findings, which add to growing evidence linking herpes viruses to neurodegenerative diseases, also turn the spotlight on the second virus that causes chickenpox.
For more than half a century, the idea that microbial infections are causative factors in neurodegenerative diseases has lingered on the fringes of neuroscience. In the 1980s, some studies linked the onset of Alzheimer's disease to infection with the herpes simplex virus, but exactly how this very common virus affects neurodegenerative diseases was unclear.
An important 2020 study by a Tufts University team demonstrated exactly how herpes virus infection induces several pathological features of Alzheimer's disease. The study used a new three-dimensional bioengineered brain model filled with neural stem cells in a sponge-like structure that can be coaxed into a variety of brain cells.
This model of brain tissue is novel, and the findings are the first to clearly show how common viral infections contribute to pathological symptoms of Alzheimer's disease. However, there is a big problem with the study results. Considering that more than two-thirds of the world's population carries herpes simplex virus type 1 (HSV-1), there must be other factors that can reactivate dormant viruses, setting off the cascade of events that lead to Alzheimer's disease.
Then, in 2022, a study looked at another common virus linked to Alzheimer's disease, varicella-zoster virus (VZV). This virus causes chickenpox and, later in life, shingles. So the researchers used the same three-dimensional bioengineered brain model to study whether VZV infection affects brain cells that have seeded dormant herpes viruses.
Interestingly, the study found that exposing brain cells carrying dormant HSV-1 to VZV caused the herpes virus to reactivate and trigger a cascade of toxic plaques known to be signs of Alzheimer's disease. However, when brain cells were exposed to VZV in the absence of the herpes virus, all of these Alzheimer's symptoms did not appear.
Dana Cairns (2022), a researcher on the project, said: "This is a slap in the face for two very common and usually harmless viruses, but laboratory studies show that if new exposure to VZV awakens dormant HSV-1, they can cause trouble."
While this study does confidently suggest that this two-pronged viral mechanism may cause Alzheimer's disease, it also makes clear that it is likely just one of many disease-causing pathways. If reactivating dormant HSV-1 can trigger the progression of Alzheimer's disease, there may be multiple pathways besides exposure to VZV.
Cairns added: "It is still possible that other infections and other causal pathways contribute to Alzheimer's disease, and risk factors such as head trauma, obesity or alcohol consumption suggest they may be intertwined when HSV re-emerges in the brain."
The study also speculates that the COVID-19 pandemic may cause Alzheimer's problems in the future, as SARS-CoV-2 infection is known to reactivate dormant VSV and HSV-1 infections. It has been suggested that the pandemic may increase the incidence of neurodegenerative diseases in the future, and the researchers behind the new study urge clinicians to pay close attention to older patients in the coming years.
Since the landmark study linked the two viruses to Alzheimer's, other findings have added weight to the link. In 2024 alone, a staggering four separate studies reported a link between reduced dementia rates and herpes vaccination. That same year, another study found a link between getting the shingles vaccine and a lower risk of dementia.