Research 'most compelling evidence ever' of viral trigger for Alzheimer's

Jun 23, 2018, 02:46
Research 'most compelling evidence ever' of viral trigger for Alzheimer's

A new study from a team at the Icahn School of Medicine at Mount Sinai has revealed an unexpected correlation between Alzheimer's disease and high levels of human herpes virus DNA. Herpes virus can lie dormant and then re-activate when someone's immune system is down, so it's not clear if the viruses cause Alzheimer's or if they re-activate as the disease progresses. One of the primary questions is whether such pathogens play an active, causative role in the disease or enter the brain simply as opportunistic passengers, taking advantage of the neural deterioration characteristic of AD.

The research team had been mapping and comparing the biological networks that underlie Alzheimer's disease, based on detailed genetic analyses of more than 600 brain tissue samples. "Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also hard to resolve".

The test centre at Waterford Institute of Technology was pioneered by Cambridge University academic Dr Alan Howard in a trial that studied people diagnosed with Alzheimer's Disease from a mild to advanced stage.

More evidence for controversial theory that herpesviruses play role in Alzhiemer's disease [news release].

"Our work identified specific biological networks that offer new testable hypotheses regarding the role of microbial defence and innate immune function in the pathophysiology of Alzheimer's". 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. But we were able to perform a more sophisticated computational analysis using multiple levels of genomic information measured directly from affected brain tissue.

The Dudley Laboratory at the Icahn School of Medicine at Mount Sinai has an institutional partnership with Banner-ASU Neurodegenerative Disease Research Center. This particular set of herpes viruses is common.

Like other herpes viruses, HHV moves to nerve cells, especially to a part of the brain called the hippocampus, Gandy said. Instead, what ultimately stood out to them were not any particular human genes but in fact an abundance of genes related to two particular strains of herpes virus. "This includes several regulators of APP [amyloid precursor protein] processing and AD-risk-associated genes".

"The title of the talk that I usually give is, 'I Went Looking for Drug Targets and All I Found Were These Lousy Viruses, '" explains Joel Dudley, co-senior author on the study. "It could be that viruses act through genes". "We saw a key virus, HHV-6A, regulating the expression of quite a few AD risk genes and genes known to regulate the processing of amyloid, a key ingredient in AD neuropathology".

The networks described suggest that the hallmarks of AD may arise as collateral damage caused by the brain's response to viral insult.

Around 850,000 people are living with dementia in Ireland and Britain, and the majority of people have Alzheimer's which occurs when sticky plaques of amyloid build up in the brain, killing brain cells.

The researchers were particularly interested in the microRNA (miRNA) miR-155, which has previously been linked with neuropathologic features of AD.

HSV-1 is a different virus from HHV-6A and HHV-7, but Dudley's team did also find that Alzheimer's brains had higher than normal levels of genetic material associated with HSV-1. "And if viral infections are playing a part, they are not the sole actor". "What I believe is that in genetically or physiological susceptible individuals, the virus is acting as an agonist of the disease", Dudley says-a number of processes likely participate, with viruses being just one piece of the puzzle.

Study author Professor Dr Sam Gandy added: "This is the most compelling evidence ever presented that points to a viral contribution to the cause or progression of Alzheimer's".

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