New evidence that viruses may play a role in Alzheimer's

Ebony Scott
June 23, 2018

"While the findings indicate a link between the activity of these viruses and Alzheimer's, they don't tell us whether they contribute to the development of the disease, help the brain to cope with the disease, or just occur alongside Alzheimer's-processes without having an impact on the health of the brain", says David Reynolds, Chief Scientific Officer of Alzheimer's Research UK.

Joel Dudley, a geneticist and genomic scientist at the Icahn School of Medicine at Mount Sinai and senior author of the new paper, had not meant to investigate this theory when his lab began working on the newly published study in 2013.

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. The higher abundance of these viruses in AD-affected brains may initiate an immune cascade leading to deterioration and cell death or act in other ways to promote AD.

They then tried to determine whether viruses are involved in the progression to Alzheimer's or whether they are, instead, bystanders or somehow consequences of the disease; it might have been the case, for instance, that people with Alzheimer's were more susceptible to viral infections.

Two common herpes viruses appear to play a role in Alzheimer's disease.

There are multiple points of overlap between virus-host interactions and genes associated with Alzheimer's risk.

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The team found viral genetic material at far higher levels in Alzheimer's-affected brains than in normal ones. Cold sores and genital herpes are common examples, as is the varicella virus that causes chickenpox in childhood and painful shingles in adults. 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. "We didn't have a horse in this virus race whatsoever".

He said the research makes a viral connection much more plausible but cautioned that the study won't affect how today's patients are treated. These viruses are carried by nearly everyone and are best known for causing a skin rash in toddlers, but they can also get into the brain.

For the new study, which was broadly created to map and compare genetic, transcriptional, and protein networks underlying AD, the team analyzed whole exome DNA and RNA sequencing data from 622 brain donors with early- and later-stage clinical and neuropathological features of AD, and another 322 brains from donors without the disease, generated through the National Institutes of Health (NIH)-sponsored Accelerated Medicines Partnership for Alzheimer's Disease (AMP-AD). "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", says Readhead.

They found that human herpesvirus 6A and 7 were up to twice as abundant in Alzheimer's disease samples than non-Alzheimer's ones. Further study into how these particular viruses interacted with human genes revealed they may disrupt a gene galled Mir155.

For more information on going purple for "The Longest Day", or for resources for families with Alzheimer's, head to the Alzheimer's Association's website here. He says the finding is important but not conclusive. So the Institute on Aging is funding a study that will test this approach.

The research community has been seeking new insights into the pathology of Alzheimer's because decades of research and hundreds of failed clinical trials have only resulted in disagreements about its underlying biology-and no new treatments have emerged to modify the course of the memory-robbing disease. So Hodes says it might be possible to protect the brain with drugs that tweak the brain's immune system.

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