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Herpes Virus May Play Role in Alzheimer’s Disease

— Roles of genes, viruses may not be 'as binary as we thought,' says researcher

Ƶ MedicalToday

Common viral species, particularly herpesviruses, may play a role in Alzheimer's disease, new research suggests.

Human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) were found in postmortem Alzheimer's disease samples at levels up to twice as high as non-Alzheimer's disease samples, Ben Readhead, MBBS, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues reported in .

Moreover, HHV-6A and HHV-7 DNA may regulate the expression of genes linked to Alzheimer's disease risk, they suggested.

"It's conceivable there are ways in which viruses interact that we haven't really taken very seriously before, in terms of provoking the pathology or the expression of disease," senior author Sam Gandy, MD, PhD, told Ƶ. "It could be that things are not as binary as we thought, that viruses act one way and genes another. It could be that viruses act through genes."

While viruses and bacteria have been implicated in population studies of Alzheimer's disease, this is the first research to use advanced genomic sequencing technology directly from the brains of Alzheimer's patients to measure viruses and build a network to see how they may influence Alzheimer's genes.

In this study, researchers initially performed RNA sequencing on more than 600 samples of postmortem tissue of people with and without Alzheimer's, looking to quantify which genes were present in the brain and whether any were associated with the development of the disease.

"We did not expect to be working on viruses," Gandy said. "We were looking for genes that were dysregulated during the progression of Alzheimer's disease."

"What we found was that the most dysregulated sequences were not from the brain itself, but from the genomes of HHV-6A and HHV-7," he added. "We don't know yet whether they're integrated or whether they're separate, but certainly there's a fairly robust association of these genomes in the brains of patients with Alzheimer's."

The researchers confirmed their findings with sequencing samples collected by other brain banks, including the in Florida and the at Rush University in Chicago, observing a persistent abundance of HHV-6A and HHV-7 among Alzheimer's disease patients in those cohorts, too. When they constructed networks that modeled how the viral genes and human genes interacted, they found multiple points of overlap between virus-host interactions and genes associated with Alzheimer's risk.

While this study does not demonstrate that viruses are linked causally to Alzheimer's disease, it may be the most compelling evidence pointing to a viral contribution ever presented, Gandy noted.

In their analysis, the researchers used data from brain banks and cohort studies of the Accelerating Medicines Partnership-Alzheimer's Disease () consortium, a partnership of government, industry, and nonprofit organizations.

"The robust findings by the Mount Sinai team would not have been possible without the open science data resources created by the AMP-AD program, particularly the availability of raw genomic data," Suzana Petanceska, PhD, who leads the AMP-AD Target Discovery and Preclinical Validation Project, said in a statement. "This is a great example of the power of open science to accelerate discovery and replication research."

Disclosures

The researchers were funded by the National Institute on Aging of the National Institutes of Health. They reported no competing financial interests in relation to this paper.

Postmortem brain tissue was collected through the NIH-designated NeuroBioBank System.

Primary Source

Neuron

Readhead B, et al "Multiscale analysis of independent Alzheimer's cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus" Neuron 2018; DOI: 10.1016/j.neuron.2018.05.023.