Study linking herpes and Alzheimer's rekindles debate over controversial old hypothesis
A new study from a team at the Icahn School of Medicine at Mount Sinai has revealed an unexpected correlation between Alzheimer's disease and high levels of human herpes virus DNA. The controversial results have rekindled an old hypothesis suggesting viruses may play a part in the development of this devastating degenerative disease.
In the 1950s, an idea arose in neuroscience that postulated microbial infections as the source of much neurodegenerative disease. The hypothesis was that they could be what are known as "slow virus diseases", where viral infections result in progressive destruction of neurological processes, potentially decades after an acute infection.
By the 1980s, a series of studies began to pop up specifically associating the herpes simplex virus with the onset of Alzheimer's disease. While a group of dedicated scientists continued to toil away at investigations correlating viral infections with Alzheimer's, the general research community began to focus on the amyloid hypothesis as the fundamental causal explanation behind the disease.
Over the last few years, though, after a series of failed clinical trials into drugs designed to attack amyloid plaque build-ups, a growing community of researchers has resurrected this old hypothesis. Some studies have even tried to build a bridge between the two hypotheses, suggesting amyloid aggregation in the brain is stimulated by microbial infection.
A robust and sophisticated new study has now exploded onto the scene, rekindling the viral hypothesis for Alzheimer's through an accidental discovery. The researchers initially set out to comprehensively examine DNA, RNA and protein footprints in the brains of deceased Alzheimer's patients with the goal of identifying certain overactive genes in Alzheimer's sufferers that could help direct future drug research. Instead, what ultimately stood out to them were not any particular human genes but in fact an abundance of genes related to two particular strains of herpes virus.
"The title of the talk that I usually give is, 'I Went Looking for Drug Targets and All I Found Were These Lousy Viruses,'" explains Joel Dudley, co-senior author on the study. "We didn't set out to find what we found. Not even close. We were trying to find drugs that could be repurposed to treat Alzheimer's patients, but the patterns that emerged from our data-driven analysis all pointed towards these viral biology themes."
The study homed in on two specific herpes viral strains that were most specifically abundant in the brains of Alzheimer's sufferers, HHV-6A and HHV-7. Further study into how these particular viruses interacted with human genes revealed they may disrupt a gene galled Mir155. When the depletion of Mir155 was modeled in mouse studies a greater accumulation of amyloid plaques was identified, suggesting a potential mechanism between the virus and commonly hypothesized Alzheimer's pathology.
"I don't think we can answer whether herpesviruses are a primary cause of Alzheimer's disease," says Dudley. 'But what's clear is that they're perturbing networks and participating in networks that directly accelerate the brain towards the Alzheimer's topology."
The research is undoubtedly compelling, but not everyone in the scientific community is convinced it means much. One of the big discordancies the study raises is that these two particular herpes viruses are profoundly common in most human beings. In fact, in North America it is estimated that 90 percent of children have at least one of these viruses in their blood early in life. So, while the connection found in this research is intriguing, it cannot draw a clear line between the presence of the virus and the onset of Alzheimer's.
"While the findings indicate a link between the activity of these viruses and Alzheimer's, they don't tell us whether they contribute to the development of the disease, help the brain to cope with the disease, or just occur alongside Alzheimer's-processes without having an impact on the health of the brain," says David Reynolds, Chief Scientific Officer of Alzheimer's Research UK.
Tara Spires-Jones, a dementia researcher from the University of Edinburgh, also cautions any conclusive idea that this study uncovers a causal link between herpes and Alzheimer's.
"Thus while these data are very interesting and important for future research, they do not definitively support the idea that people with herpes are more likely to develop Alzheimer's." says Spires-Jones.
Dudley, on the other hand, is much more convinced that his team's research should be directing other scientists toward a deeper exploration into the viral hypothesis.
"We didn't have a horse in this virus race whatsoever," says Dudley. "It's the data that took us there. And now, not only is the viral hypothesis resurrected: it has specific testable pathways and networks and interactions that can be explored and reconciled with the rest of the work emerging in Alzheimer's."
The study was published in the journal Neuron.