From: 23x12c@gmail.com   
      
   ScienceDaily   
   Your source for the latest research news   
      
   Science News from research organizations   
      
   More evidence for controversial theory that herpesviruses play role in   
   Alzheimer's disease   
   Date:   
   June 21, 2018   
   Source:   
   Cell Press   
   Summary:   
   In a large-scale analysis, researchers use data from three different brain   
   banks to suggest that human herpesviruses are more abundant in the brains of   
   Alzheimer's patients and may play a role in regulatory genetic networks that   
   are believed to lead to    
   the disease. This work lends support to the controversial hypothesis that   
   viruses are involved in Alzheimer's disease and offers potential new paths for   
   treatment.   
   Share:   
           
   FULL STORY   
      
   The brain is shown here as a complex network of interactions, with disruption   
   of connections by the key viral species (HHV-6A, HHV-6B, HHV-7) identified in   
   this study.   
   Credit: Readhead et al.   
   The quest to understand what causes Alzheimer's disease -- and to treat it --   
   is complicated by the disease's long, slow progression and the difficulty of   
   collecting brain tissue samples. But in a large-scale analysis published June   
   21 in the journal    
   Neuron, researchers at the Icahn School of Medicine at Mount Sinai use data   
   from three different brain banks to suggest that human herpesviruses are more   
   abundant in the brains of Alzheimer's patients and may play a role in   
   regulatory genetic networks    
   that are believed to lead to the disease. This work lends support to the   
   controversial hypothesis that viruses are involved in Alzheimer's disease and   
   offers potential new paths for treatment.   
      
   advertisement   
      
   "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," says co-senior author and   
   geneticist Joel Dudley. who is also a member of the ASU-Banner N   
   urodegenerative Disease Research Center.   
      
   The researchers analyzed 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.   
      
   "This kind of analysis was only possible because the consortium had   
   coordinated for all of these other groups to put their sequencing data in the   
   AMP-AD Knowledge Portal in a precompetitive environment that let us very   
   quickly replicate our work across    
   all these different cohorts. We needed access to sequences that are usually   
   discarded in the course of studying the human genome. We needed to search for   
   sequences from hundreds of different viruses, so having access to that raw,   
   unprocessed data was    
   absolutely key," says first author Ben Readhead.   
      
   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 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.   
      
   "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," says 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 defense   
   against infections. In their study, they found that herpesviruses were   
   involved in networks that regulate amyloid precursor proteins.   
      
   They argue, however, that their work shouldn't make anyone worried. "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," says 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. "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.   
      
   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. "We didn't have a horse in this virus race   
   whatsoever. It's the data that took    
   us there. And now, not only is the viral hypothesis resurrected: it has   
   specific testable pathways and networks and interactions that can be explored   
   and reconciled with the rest of the work emerging in Alzheimer's," says Dudley.   
      
   "All these Alzheimer's brains in these separate, major brain banks have   
   previously unsuspected substantial populations of herpesvirus genomes and that   
   deserves an explanation wherever it falls in the pathogenesis. It doesn't   
   deserve to just be brushed    
   away," says Gandy.   
      
   advertisement   
      
      
   [continued in next message]   
      
   --- SoupGate-Win32 v1.05   
    * Origin: you cannot sedate... all the things you hate (1:229/2)