Analysis of large data sets from post-mortem brain samples of people with and without Alzheimer's disease has revealed new evidence that viral species, particularly herpesviruses, may have a role in Alzheimer's disease biology. Researchers funded by the National Institute on Aging (NIA), part of the National Institutes of Health, made the discovery by harnessing data from brain banks and cohort studies participating in the Accelerating Medicines Partnership - Alzheimer's Disease (AMP-AD) consortium.
Reporting in the June 21 issue of the journal Neuron, the authors emphasize that their findings do not prove that the viruses cause the onset or progression of Alzheimer's. Rather, the findings show viral DNA sequences and activation of biological networks--the interrelated systems of DNA, RNA, proteins and metabolites--may interact with molecular, genetic and clinical aspects of Alzheimer's.
"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," said NIA Director Richard J. Hodes, M.D. "This research reinforces the complexity of Alzheimer's disease, creates opportunities to explore Alzheimer's more thoroughly, and highlights the importance of sharing data freely and widely with the research community."
Alzheimer's disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks. More evidence is accumulating to indicate that this loss of cognitive functioning is a mix of many different disease processes in the brain, rather than just one, such as buildup of amyloid or tau proteins. Identifying links to viruses may help researchers learn more about the complicated biological interactions involved in Alzheimer's, and potentially lead to new treatment strategies.
The research group, which included experts from Icahn School of Medicine at Mount Sinai, New York City, and Arizona State University, Phoenix, originally set out to find whether drugs used to treat other diseases can be repurposed for treating Alzheimer's. They designed their study to map and compare biological networks underlying Alzheimer's disease. What they found is that Alzheimer's biology is likely impacted by a complex constellation of viral and host genetic factors, adding that they identified specific testable pathways and biological networks.
"The robust findings by the Mount Sinai team would not have been possible without the open science data resources created by the AMP-AD program-particularly the availability of raw genomic data," said NIA Program Officer Suzana Petanceska, Ph.D., who leads the AMP-AD Target Discovery and Preclinical Validation Project. "This is a great example of the power of open science to accelerate discovery and replication research."
The researchers used multiple layers of genomic and proteomic data from several NIA-supported brain banks and cohort studies. They began their direct investigation of viral sequences using data from the Mount Sinai Brain Bank and were able to verify their initial observations using datasets from the Religious Orders Study, the Memory and Aging Project and the Mayo Clinic Brain Bank. They were then able to incorporate additional data from the Emory Alzheimer's Disease Research Center to understand viral impacts on protein abundance. Through the application of sophisticated computational modeling the researchers made several key findings, including:
- Human herpesvirus 6A and 7 were more abundant in Alzheimer's disease samples than non-Alzheimer's.
- There are multiple points of overlap between virus-host interactions and genes associated with Alzheimer's risk.
- Multiple viruses impact the biology of Alzheimer's disease across domains such as DNA, RNA and proteins.
Important roles for microbes and viruses in Alzheimer's disease have been suggested and studied for decades, the authors noted. Since the 1980s, hundreds of reports have associated Alzheimer's with bacteria and viruses. These studies combined suggest a viral contribution but have not explained how the connection works.
While the current findings are more specific, they do not provide evidence to change how risk and susceptibility are assessed, nor the diagnosis and treatment of Alzheimer's, the authors said. Rather, the research gives scientists reason to revisit the old pathogen hypothesis and will be the basis for further work that will test whether herpes virus activity is one of the causes of Alzheimer's.
Readhead et al. Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron. 2018 Jun. 21. Doi: 10.1016/j.neuron.2018.05.023
Grants include: AG046139, EB020406, AG016574, AG032990, AG046139, AG018023, AG006576, AG006786, AG025711, AG017216, AG003949, NS080820, NS072026, AG19610, AG10161, AG15819, AG17917, AG30146, AG36836, AG32984 and AG46152.
This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process--each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.
About AMP-AD: The Accelerating Medicines Partnership is a joint venture among the National Institutes of Health, the Food and Drug Administration, 12 biopharmaceutical and life science companies and 13 non-profit organizations, managed by the Foundation for the NIH, to identify and validate promising biological targets of disease. AMP-AD is one of the four initiatives under the AMP umbrella; the other three are focused on type 2 diabetes (AMP-T2D), rheumatoid arthritis and systemic lupus erythematosus (AMP-RA/SLE) and Parkinson's disease (AMP-PD). The AMP-AD knowledge portal already has over 1,300 total users. To learn more about the AMP-AD Target Discovery and Preclinical Validation Project please visit: https:/
About the National Institute on Aging: The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. The NIA is designated as the lead NIH institute for information on Alzheimer's disease. It provides information on age-related cognitive change and neurodegenerative disease, including participation in clinical studies, specifically on its Alzheimer's website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.
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