There is mounting evidence that links neurodegenerative diseases and viral infections, such as the association between multiple sclerosis and Epstein-Barr virus. Studies have also revealed significant links between viral infections and Alzheimer's disease. The strongest connection is between Alzheimer's and herpes simplex virus-1, which is a common virus. HSV-1 is also known to cause encephalitis in some cases, and DNA from HSV-1 has been associated with problems in the brain that are related to Alzheimer's.
However, while there is evidence of HSV-1 in cerebrospinal fluid from Alzheimer's patients, there has been no evidence of active infection, or HSV-1 virions in the brain. In a new study, researchers set out to learn more about whether HSV-1 proteins are being expressed, but at levels that are lower than in active infection, in the Alzheimer's brain.
This study showed, using a variety of techniques, that HSV-1 proteins are indeed present in brain samples from Alzheimer's patients and in organoid models of the disease. Aberrant tau proteins, which are one hallmark of Alzheimer's disease, were also found along with HSV-1 proteins in parts of the brain that are disrupted in Alzheimer's. The findings have been published in Cell Reports.
The work also showed that HSV-1 proteins may alter the tau protein (by phosphorylating it), which may affect how tau functions. This link seems to have an intially protective effect on neurons that are virally infected, which may indicate that tau is related to immune responses in the brain.
The HSV-1 proteins did not associate with another hallmark of Alzheimer's disease known as amyloid plaques.
"Our study challenges the conventional view of tau as solely harmful, showing that it may initially act as part of the brain's immune defense," said senior study author Or Shemesh, PhD, an assistant professor at University of Pittsburgh. "These findings emphasize the complex interplay between infections, immune responses, and neurodegeneration, offering a fresh perspective and potential new targets for therapeutic development."
Interstingly, a study reported in Nature Neuroscience last year also determined that tau can have a protective effect in the brain; it helps shield against the damage that can be caused by reactive oxygen species.
There is still a lot more to learn about how Alzheimer's disease arises and progresses. This research group is planning to continue to investigate the link between HSV-1 and Alzheimer's disease, and look for potential treatments that may take aim at viral infections in the brain. They also want to know more about how viral infections might relate to other neurodegenerative conditions.
Sources: University of Pittsburgh, Cell Reports
