When the Taiwanese authors looked at subjects who suffered severe herpes infection and who were treated aggressively with antiviral drugs, the relative risk of dementia was reduced by a factor of 10.
http://dgnews.docguide.com/unusually-high-levels-herpes-viruses-found-brains-patients-alzheimer-s-disease?
NEW
YORK -- June 26, 2018 -- Researchers have discovered that 2 strains of
human herpesvirus -- human herpesvirus 6A (HHV-6A) and human herpesvirus
7 (HHV-7) -- are found in the brains of people with Alzheimer’s disease
at levels up to twice as high as in those without Alzheimer’s.
In a study published in Neuron, Benjamin Readhead, Icahn School of Medicine at Mount Sinai, New York, New York, and colleagues described how they used evidence from postmortem brain tissue to identify previously unknown gene networks that will offer new testable hypotheses for understanding Alzheimer’s pathology and reveal novel potential targets for new drugs that may halt Alzheimer’s disease progression.
The researchers initially performed RNA sequencing on 4 brain regions (superior temporal gyrus, anterior prefrontal cortex, inferior frontal gyrus, and parahippocampal gyrus) in over 600 samples of postmortem tissue from people with and without Alzheimer’s to quantify which genes were present in the brain, and whether any were associated with the onset and progression of Alzheimer’s.
Through a variety of computational approaches, the team uncovered a complex network of unexpected associations, linking specific viruses with different aspects of Alzheimer’s biology. They examined the influence of each virus on specific genes and proteins in brain cells, and identified associations between specific viruses and amyloid plaques, neurofibrillary tangles, and clinical dementia severity.
Notably, the study found an abundance of HHV-6A and HHV-7 across the anterior prefrontal cortex and the superior temporal gyrus.
To evaluate the robustness of their findings, the researchers incorporated over 800 additional RNA sequencing samples from 2 additional, independent cohorts and were able to replicate their main findings.
“This study represents a significant advancement in our understanding of the plausibility of the pathogen hypothesis of Alzheimer’s,” said Joel Dudley, PhD, Icahn School of Medicine at Mount Sinai. “Our work identified specific biological networks that offer new testable hypotheses regarding the role of microbial defense and innate immune function in the pathophysiology of Alzheimer’s. If it becomes evident that specific viral species directly contribute to an individual’s risk of developing Alzheimer’s or their rate of progression once diagnosed, then this would offer a new conceptual framework for understanding the emergence and evolution of Alzheimer’s at individual, as well as population, levels.”
The findings could translate to the identification of virus, or virus-related, biomarkers that may improve patient risk stratification and diagnosis, noted Dr. Dudley. It could also imply novel viral targets and biological pathways that could be addressed with new preventative and therapeutic drugs. As with any complex set of findings, they will need to be confirmed in additional patient cohorts, and further studies to specifically address a causal role for viruses are now being conducted.
“This is the most compelling evidence ever presented that points to a viral contribution to the cause or progression of Alzheimer’s,” added Sam Gandy, MD, Center for Cognitive Health and NFL Neurological Care at Mount Sinai, New York, New York. “A similar situation arose recently in certain forms of Lou Gehrig’s disease. Viral proteins were discovered in the spinal fluid of some patients [with Lou Gehrig’s disease], and patients with positive viral protein tests in their spinal fluid showed benefit when treated with antiviral drugs.”
Reference: https://doi.org/10.1016/j.neuron.2018.05.023
SOURCE: Mount Sinai Health System
In a study published in Neuron, Benjamin Readhead, Icahn School of Medicine at Mount Sinai, New York, New York, and colleagues described how they used evidence from postmortem brain tissue to identify previously unknown gene networks that will offer new testable hypotheses for understanding Alzheimer’s pathology and reveal novel potential targets for new drugs that may halt Alzheimer’s disease progression.
The researchers initially performed RNA sequencing on 4 brain regions (superior temporal gyrus, anterior prefrontal cortex, inferior frontal gyrus, and parahippocampal gyrus) in over 600 samples of postmortem tissue from people with and without Alzheimer’s to quantify which genes were present in the brain, and whether any were associated with the onset and progression of Alzheimer’s.
Through a variety of computational approaches, the team uncovered a complex network of unexpected associations, linking specific viruses with different aspects of Alzheimer’s biology. They examined the influence of each virus on specific genes and proteins in brain cells, and identified associations between specific viruses and amyloid plaques, neurofibrillary tangles, and clinical dementia severity.
Notably, the study found an abundance of HHV-6A and HHV-7 across the anterior prefrontal cortex and the superior temporal gyrus.
To evaluate the robustness of their findings, the researchers incorporated over 800 additional RNA sequencing samples from 2 additional, independent cohorts and were able to replicate their main findings.
“This study represents a significant advancement in our understanding of the plausibility of the pathogen hypothesis of Alzheimer’s,” said Joel Dudley, PhD, Icahn School of Medicine at Mount Sinai. “Our work identified specific biological networks that offer new testable hypotheses regarding the role of microbial defense and innate immune function in the pathophysiology of Alzheimer’s. If it becomes evident that specific viral species directly contribute to an individual’s risk of developing Alzheimer’s or their rate of progression once diagnosed, then this would offer a new conceptual framework for understanding the emergence and evolution of Alzheimer’s at individual, as well as population, levels.”
The findings could translate to the identification of virus, or virus-related, biomarkers that may improve patient risk stratification and diagnosis, noted Dr. Dudley. It could also imply novel viral targets and biological pathways that could be addressed with new preventative and therapeutic drugs. As with any complex set of findings, they will need to be confirmed in additional patient cohorts, and further studies to specifically address a causal role for viruses are now being conducted.
“This is the most compelling evidence ever presented that points to a viral contribution to the cause or progression of Alzheimer’s,” added Sam Gandy, MD, Center for Cognitive Health and NFL Neurological Care at Mount Sinai, New York, New York. “A similar situation arose recently in certain forms of Lou Gehrig’s disease. Viral proteins were discovered in the spinal fluid of some patients [with Lou Gehrig’s disease], and patients with positive viral protein tests in their spinal fluid showed benefit when treated with antiviral drugs.”
Reference: https://doi.org/10.1016/j.neuron.2018.05.023
SOURCE: Mount Sinai Health System
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