For the past 60 years scientists have thought microbes and viruses may play a role in the onset and progression of Alzheimer’s disease, although studies conducted to date have not uncovered sufficient evidence to suggest that is definitely the case. However, a new study suggests that two viruses could well trigger the disease or play a role in its progression.
The research team, headed by the Icahn School of Medicine at Mount Sinai, conducted a sophisticated computational analysis of genetic and molecular networks in the brains of patients with Alzheimer’s disease that suggested two species of human herpes viruses could play a significant role in the development of the disease.
The Roseoloviruses – human herpesvirus 6A (HHV6A) and 7 (HHV7) – were present at increased levels in patients with Alzheimer’s disease and were found to be interacting with gene networks in parts of the brain affected by Alzheimer’s disease.
“We were able to perform a more sophisticated computational analysis using multiple levels of genomic information measured directly from affected brain tissue,” explained Joel Dudley, Ph.D., associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai and associate research professor at the Arizona State University-Banner Neurodegenerative Disease Research Center (NDRC). “This analysis allowed us to identify how the viruses are directly interacting with or coregulating known Alzheimer’s genes.”
It is unknown whether the viruses are a primary cause of Alzheimer’s disease or whether the viruses exacerbate the disease. What is known is the viruses are participating in and altering the normal state of the networks that underlie the pathophysiology of the disease.
The research team analysed whole exome DNA and RNA sequencing data from 622 brain donors who had been diagnosed with early or late-stage Alzheimer’s disease and 322 brain donors who did not have Alzheimer’s disease.
The primary aim of the study was to identify disease mechanisms that could be targeted with drugs. The researchers initially examined transcriptomes in regions of the brain that undergo the earliest changes in Alzheimer’s disease. It was hoped they would uncover novel biology that could improve understanding of the dramatic changes seen in the later stages of the disease.
Using their computational analysis, the researchers identified genetic, transcriptional, and molecular networks that underpin Alzheimer’s disease development and progression, and how viruses may be involved.
The study revealed multiple viruses in the brains of normal aging brains; however, patients with Alzheimer’s disease had higher levels of HHV6A and HHV7. “HHV-6A and HHV-7 are not ubiquitous features of neuropathology and appear at least partially specific to AD,” wrote the researchers.
Constructed virus–host protein networks suggest HHV6A and HHV7 interaction perturbs cell nucleotide pools, tRNA synthesis, and protein translation, which the researchers suggest induced “dysregulation of nucleotide pool metabolism, especially purine bases, consistent with several metabolomics studies in AD.” The researchers note that the features of Alzheimer’s disease may be collateral damage caused by the brain’s response to the presence of the viruses.
This is the first study that has provided strong evidence to suggest that viruses play a major role in the development of brain disease.
The research is detailed in the paper – Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus – which was recently published in the journal Neuron. https://doi.org/10.1016/j.neuron.2018.05.023