Herpes Viruses May Play Role in Alzheimer’s
Human herpesviruses are more abundant in the brains of Alzheimer’s patients and may play a role in the genetic networks believed to lead to disease development, according to a new large-scale analysis conducted by researchers at the Icahn School of Medicine at Mount Sinai.
The new findings, published in the journal Neuron, support the controversial hypothesis that viruses are involved in Alzheimer’s disease, a notion that may offer potential new paths for treatment.
“The title of the talk that I usually give is, ‘I Went Looking for Drug Targets and All I Found Were These Lousy Viruses’,” said co-senior author and geneticist Dr. Joel Dudley, who is also a member of the Arizona State University (ASU)-Banner Neurodegenerative Disease Research Center.
“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 researchers analyzed data from three major brain banks courtesy of the National Institutes of Health’s Accelerating Medicines Partnership — Alzheimer’s Disease (AMP-AD) consortium. This allowed them to look at raw genomic data for large numbers of Alzheimer’s patients in different cohorts.
The team constructed, mapped, and compared regulatory gene networks in areas of the brain known to be affected by Alzheimer’s on multiple levels, looking at DNA, RNA, and proteins.
“We needed to search for sequences from hundreds of different viruses, so having access to that raw, unprocessed data was absolutely key,” said first author Ben Readhead, M.B.B.S.
The findings reveal that human herpes virus DNA and RNA were more abundant in the brains of deceased patients who had been diagnosed with Alzheimer’s disease and that abundance correlated with clinical dementia scores.
Importantly, the two viruses most strongly associated with Alzheimer’s — HHV-6A and HHV-7 — were not as abundant in the brains of those with other neurodegenerative disorders. When the researchers constructed networks that modeled how the viral genes and human genes interacted, they were able to show that the viral genes were regulating and being regulated by the human genes, and that genes associated with increased Alzheimer’s risk were affected.
“I don’t think we can answer whether herpes viruses are a primary cause of Alzheimer’s disease. But what’s clear is that they’re perturbing networks and participating in networks that directly accelerate the brain towards the Alzheimer’s topology,” said Dudley.
The researchers believe their findings align with other Alzheimer’s studies focused on the role of innate immunity in the disease, particularly recent findings that beta-amyloid protein — the culprit behind the plaques that build up in the Alzheimer’s-affected brain — may accumulate as part of a defense against infections. In fact, in the current study, the researchers found that herpes viruses were involved in networks that regulate amyloid precursor proteins.
The researchers assert that their work shouldn’t make anyone worried, however.
“While these findings do potentially open the door for new treatment options to explore in a disease where we’ve had hundreds of failed trials, they don’t change anything that we know about the risk and susceptibility of Alzheimer’s disease or our ability to treat it today,” said co-senior author and Alzheimer’s disease specialist Dr. Sam Gandy.
This is especially true since the herpes viruses HHV-6A and HHV-7 are extremely common and often latent or asymptomatic. In North America, for example, nearly 90 percent of children have one of these viruses circulating in their blood by the time they’re a few years old.
“There are still a lot of unanswered questions around how we go from being able to detect it circulating in someone’s blood to knowing whether it’s active in a state that might be relevant to Alzheimer’s disease,” said Readhead.
Still, the new findings offer strong support for a long-controversial hypothesis that viruses might be involved in the development of Alzheimer’s disease.
“We didn’t have a horse in this virus race whatsoever,” said 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.”
Gandy added, “All these Alzheimer’s brains in these separate, major brain banks have previously unsuspected substantial populations of herpes virus genomes and that deserves an explanation wherever it falls in the pathogenesis. It doesn’t deserve to just be brushed away.”
Source: Cell Press
Pedersen, T. (2018). Herpes Viruses May Play Role in Alzheimer’s. Psych Central. Retrieved on November 23, 2020, from https://psychcentral.com/news/2018/07/02/herpes-viruses-may-play-role-in-alzheimers/136674.html