Researchers Find Herpes Viruses In Brains Marked By Alzheimer's Disease

Researchers Find Herpes Viruses In Brains Marked By Alzheimer's Disease

Brains riddled with Alzheimer's disease contain high levels of two strains of human herpes virus, researchers discovered.

"The hypothesis that viruses play a part in brain disease is not new, but this is the first study to provide strong evidence based on unbiased approaches and large data sets that lends support to this line of inquiry", National Institute on Aging director Richard J. Hodes, MD, said in a statement.

The research group, including experts from Icahn School of Medicine at Mount Sinai and Arizona State University, performed RNA sequencing on four brain regions in more than 600 samples of postmortem tissue from people with and without Alzheimer's to quantify which genes were present in the brain.

The nature and significance of viruses and other pathogens in the brain are now hot topics in neuroscience, though the exploration is still in its early stages.

The new study went farther: Researchers used computer models to check how the viral genes interacted with human genes, proteins and amyloid buildup, nearly like the viruses' social media connections, Dudley explained. They designed their study to map and compare biological networks underlying Alzheimer's disease. "Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also hard to resolve".

There may be some new clues as to what lead to Alzheimer's Disease. It seems feasible that amyloid is not the cause of disease in many cases.

The goal was to identify new targets for drugs.

The researchers used multiple layers of genomic and proteomic data from several NIA-supported brain banks and cohort studies.

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Dudley and his colleagues stumbled across this possible viral link to Alzheimer's during an analysis meant to find ways that drugs used to treat other illnesses could be repurposed for treating the dreaded neurodegenerative disease. They infect almost every human, typically during infancy, and have been closely linked to the childhood rash called roseola, according to the HHV-6 Foundation. Scientists have linked some herpes viruses to Alzheimer's Disease.

One of the primary questions is whether such pathogens play an active, causative role in the disease or enter the brain simply as opportunistic passengers, taking advantage of the neural deterioration characteristic of Alzheimer's disease.

The investigators found that the Alzheimer's disease process is likely affected by a complex series of interactions between viral and human genetics. "HHV-6A stood out as a notable", they state, and exhibited a significant overlap between the set of host genes it collectively induced across all tissues and AD-associated genes. "Look, my life would be easier, too, if we hadn't found these viruses", he says.

The team found viral genetic material at far higher levels in Alzheimer's-affected brains than in normal ones. When they 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 impacted.

The networks described suggest that the hallmarks of AD may arise as collateral damage caused by the brain's response to viral insult. Some studies have even tried to build a bridge between the two hypotheses, suggesting amyloid aggregation in the brain is stimulated by microbial infection.

The researchers were particularly interested in the microRNA (miRNA) miR-155, which has previously been linked with neuropathologic features of AD.

"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. "And if viral infections are playing a part, they are not the sole actor". "This is is also consistent with the contribution of viral perturbation in driving the preclinical AD transcriptional phenotype, given that our prioritization of miR-155 was informed by findings in the preclinical AD networks".

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