Unusually High Levels Of Herpesvirus In Brains With Alzheimer’s1 year, 5 months ago
Posted on Jun 25, 2018, 4 p.m.
Human herpesvirus 6A and 7 have been found to be up to twice as high in levels within the brains of patients with Alzheimer’s disease, according Mount Sinai researchers. The team has previously identified an unknown gene network that will offer new testable hypotheses for understanding pathology and development of novel potential drug targets which may arrest the disease progression and prevention, as published in Neuron.
A data driven approach was used to study impacts of viruses on the disease to identify the roles of human herpesvirus 6A and 7, results provided first evidence of integration of HHV genomes into human brain genomes playing roles in the etiology of Alzheimer’s disease; these viruses are known to be able to cause encephalitis and other chronic conditions.
RNA sequencing was initially performed on four brain regions in over 600 postmortem tissue samples from over 600 people with and without the disease to quantify which genes were present and whether any were associated with onset and progression of Alzheimer’s disease. Computational approaches were used to uncover an unexpected complex network of associations linking specific viruses with different aspects of the disease biology. Influence of each virus on specific genes and brain cell proteins were examined to identify associations between specific amyloid plaques and viruses, neurofibrillary tangles and clinical dementia severity. Robustness of findings was evaluated by incorporating an additional 800 RNA sequencing samples from the Mayo Clinic and Rush ALzheimer’s Disease Center observing persistent increases of HHV-6A and HHV-7 abundance in Alzheimer’s samples, replicating main findings in two independent, additional, geographically dispersed cohorts.
It is estimated that every 65 seconds someone within the USA develops Alzheimer’s disease, costs to providing care are around $277 billion. New diagnosis could occur every 33 seconds by midcentury with costs expected to exceed $1 trillion annually. Alzheimer’s disease remains in the top 10 cases of mortality within the USA for which there are no disease modifying treatments available.
Extensive molecular profiling of several large cohorts enabled this study generated from NIA, AMP-AD, and NIH. Generation of the large multi-omic resource enabled the team to perform investigations of viral activity in Alzheimer’s that was entirely data driven, and represents a significant advancement of understandings of plausibilities of pathogen hypothesis of the disease, according to the researchers. Specific biological networks were identified which can offer testable hypotheses in regards to roles of microbial defense and innate immune function in Alzheimer’s pathophysiology, which could possibly potentially translate to identification of virus or virus related biomarkers which may improve patient risk stratification, diagnosis, and novel targets that could be addressed with new therapeutic and preventative drugs. Results need to be confirmed in additional cohorts to specifically address the compelling evidence of causal roles for viruses, studies are currently being conducted by the team to address this.
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