Herpes link to Alzheimer's
Human herpesviruses are more abundant in the brains of Alzheimer’s patients, according to a new study.
Researchers at the Icahn School of Medicine at Mount Sinai used data from three different brain banks in the large-scale study, which lends support to the controversial hypothesis that viruses are involved in Alzheimer’s disease and offers 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’. 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,” said co-senior author and geneticist Joel Dudley.
The researchers analysed data from three major brain banks courtesy of the National Institutes of Health's Accelerating Medicines Partnership — Alzheimer’s Disease (AMP-AD) consortium, which allowed them to look at raw genomic data for large numbers of Alzheimer’s patients in different cohorts. They 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.
They found that human herpesvirus DNA and RNA were more abundant in the brains of those diagnosed postmortem with Alzheimer’s disease and that abundance correlated with clinical dementia scores. And the two viruses they found to be 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 they constructed networks that modelled 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 impacted.
“Previous studies of viruses and Alzheimer’s have always been very correlative. But we were able to do statistical causal inference testing and more sophisticated analysis, which allowed us to identify how the viruses are directly interacting with or coregulating or being regulated by Alzheimer’s genes.
“I don’t think we can answer whether herpesviruses 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 that their findings align with other current research in the Alzheimer’s field 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 defence against infections. In their study, they found that herpesviruses were involved in networks that regulate amyloid precursor proteins.
“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 Sam Gandy.
This is especially true because HHV-6A and HHV-7 are extremely common and often latent or asymptomatic: in North America, almost 90% of children have one of these viruses circulating in their blood by the time they’re a few years old.
But even if questions remain, this research offers strong support for a long-controversial hypothesis that viruses might be involved in the development of Alzheimer’s disease.
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