Provocative study shows how the herpes virus can speed up the onset of Alzheimer’s disease
An intriguing new study from researchers at Stockholm University and Karolinska Institutet has described a mechanism by which virus particles can interact with proteins in biological fluids and become more infectious, while also accelerating the formation of plaques often associated with neurodegenerative diseases such as Alzheimer's.
In the 1980s a series of studies found a strange association between the herpes simplex virus and the onset of Alzheimer's disease. It was suggested neurodegenerative disease could have a viral origin and this intriguing hypothesis sat on the fringes of neuroscience while the more popular amyloid hypothesis rose to common consensus by the end of the century.
Following a torrent of failed clinical trials, testing drugs designed to directly attack the buildup of amyloid plaques, some researchers are now reconsidering these alternative viral hypotheses. One of the big challenges in furthering the viral association with Alzheimer's disease has been understanding what possible mechanism could cause a virus such as herpes to accelerate neurodegenerative decline.
A new research paper investigating the ways viruses can interact with proteins has, for the first time, demonstrated how certain viruses may be able to accelerate the progression of Alzheimer's disease. The study describes how viruses can become coated in different layers of proteins depending on the biological fluid they inhabit. This protein layer is known as a protein corona, and the effects of a specific protein corona can vary depending on the given protein environment surrounding the virus.
"Imagine a tennis ball falling into a bowl of milk and cereals," says Kariem Ezzat, lead author on the new study. "The ball is immediately covered by the sticky particles in the mix and they remain on the ball when you take it out of the bowl. The same thing happens when a virus gets in contact with blood or lung fluids that contain thousands of proteins. Many of these proteins immediately stick to the viral surface forming a so-called protein corona."
One of the viruses studied in the research was herpes simplex virus type 1 (HSV-1). Despite a growing body of associational evidence connecting HSV-1 to the aggregation of amyloid plaques and the onset of Alzheimer's, it has been unclear exactly how the virus could be inducing this pathology. The new research revealed that HSV-1 has the ability to catalyze amyloid proteins in its corona and induce the aggregation of those proteins. Essentially, the virus cells help speed up the formation of amyloid proteins into larger plaque accumulations.
To verify the mechanism in living organisms, the researchers looked at a mouse model engineered to rapidly develop amyloid Alzheimer's pathology. Some of the animals were intracranially infected with HSV-1 and the results were stark. The infected animals developed notable pathological signs of Alzheimer's within 48 hours, whereas uninfected mice would normally take several months to reach that same degenerative point.
The researchers are cautious to specify the study does not prove causality between the virus and Alzheimer's disease, but instead it offers a compelling mechanistic explanation as to why many associational studies have found these correlations. Due to the profoundly common nature of HSV-1 infections in human beings it is incredibly unlikely the virus is solely responsible for the onset of Alzheimer's. However, this may be one important factor that can speed up the disease's progression in individuals with other yet to be discovered risk factors.
"… describing a physical mechanism that links viral and amyloid causes of disease adds weight to the increasing research interest in the role of microbes in neurodegenerative disorders such as Alzheimer's disease and opens up new avenues for treatments," concludes Ezzat.
The new study was published in the journal Nature Communications.
Source: Stockholm University