Viruses May Play a Role in Alzheimer’s Disease

by Inside Mt. Sinai:Two strains of human herpesvirus—human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7)—are found in the brains of individuals with Alzheimer’s disease at levels up to twice as high as in those without Alzheimer’s, according to findings published June 21, 2018, in Neuron by a team of Icahn School of Medicine at Mount Sinai researchers.These common viruses, best known for causing roseola, a skin rash in children, can also be present in the brain and remain inactive for years. They also can cause encephalitis and other chronic disorders.It is the first study to use an entirely data-driven approach to examine the impact of viruses on Alzheimer’s—and to identify potential disease-associated roles of these particular viruses, which was an unexpected discovery.The researchers had been comparing genetic data in healthy and postmortem Alzheimer’s brains to identify possible new drug targets for Alzheimer’s disease when their complex computations revealed the unusually high levels of the viral genomes.“This study represents a significant leap forward in our understanding of how viruses may play a role in Alzheimer’s disease,” says the study’s senior author, Joel Dudley, PhD, Mount Sinai Professor in Biomedical Data Science, and the Director of the Icahn School of Medicine’s Institute for Next Generation Healthcare. “We were able to not only measure these viruses using computational techniques but also build out the networks in which these viruses are operating and influencing known Alzheimer’s genes.”The study was enabled in part by powerful new molecular profiling data released by the National Institute on Aging (NIA) Accelerating Medicines Partnership-Alzheimer’s Disease, a collaboration among industry, government, and nonprofit organizations dedicated to identifying new targets for preventing or treating the disease. Using those data, the team conducted computer mapping of four brain regions from more than 600 samples from the Mount Sinai Brain Bank, which for the last 36 years has been examining postmortem brain tissue from donors for Alzheimer’s-related research.As the study progressed, the team found the higher levels of HHV6A and HHV7 viruses, which was subsequently confirmed using data from brain banks in three other major NIA Alzheimer’s Centers. Researchers also discovered that the viruses appeared to accelerate the development of Alzheimer’s-related plaques and tangles in the brain.“Our team was initially quite skeptical about these findings,” says the study co-senior author, Sam Gandy, MD, PhD, Mount Sinai Professor in Alzheimer’s Research and the Director of the Center for Cognitive Health and NFL Neurological Care at Mount Sinai. “Gradually, we became convinced that what we were seeing is a real property of Alzheimer’s brains in several internationally recognized brain banks, and that we ought to report it, even if we cannot completely explain what these viruses are doing in the brain.”Although the study does not prove a direct causal role between these herpesviruses and Alzheimer’s disease, or indicate what activates the viruses, the findings do lend credence to the hypothesis that these herpesviruses may trigger progression of dementia in Alzheimer’s. This work also opens new avenues for the identification of subpopulations and biomarkers, which would not only make it easier to diagnose and determine a person’s risk of developing Alzheimer’s but also possibly create opportunities to use existing antiviral drugs and drugs that stop the brain’s immune cells from responding to these viruses.“We have been inundated with letters and emails from people sharing stories about viral infection and Alzheimer’s disease in their personal or family life, and that is an impetus for us to find an effective therapy as soon as we can,” Dr. Dudley says.Source: http://inside.mountsinai.org/blog/researchers-advance-the-understanding-of-how-viruses-may-play-a-role-in-alzheimers-disease/