What role do viruses have in Alzheimer's disease?
The researchers — including specialists from the Icahn School of Medicine at Mount Sinai in New York City, NY, and Arizona State University in Phoenix — found that the brains of people with Alzheimer's had more human herpesviruses HHV-6A and HHV-7 than the brains of people without the disease.
The new study was funded by the National Institute on Aging, which is part of the National Institutes of Health (NIH), and a paper on it is soon to be published in the journal Neuron.
The study paper describes a complex and "multiscale" investigation involving advanced computer models that draws on different levels of data. The data span evidence relating to: DNA, the RNA molecules that transcribes it, and proteins; and clinical and pathological features.
It provides compelling evidence of how viruses might be involved in "regulatory genetic networks" that scientists believe may lead to Alzheimer's disease.
But, while it supports the idea that viruses play a role, it does not show clearly whether viruses cause Alzheimer's, or whether they are merely "opportunistic passengers" of the disease process.
Nevertheless, learning more about the involvement of viruses helps to improve our knowledge of Alzheimer's disease biology and could lead to new treatments.
Dr. Richard J. Hodes, who is director of the National Institute on Aging, says that the evidence "reinforces the complexity of Alzheimer's" and should help all researchers to investigate the disease "more thoroughly."
Alzheimer's disease is on the rise
Alzheimer's is a brain-destroying disease that kills neurons, or brain cells, and gets worse over time. As it progresses, it robs us of our ability to think, remember, have conversations, contribute to society, and lead independent lives.
In the United States — where the number of people living with the disease is increasing rapidly — Alzheimer's is a leading cause of poor health and disability and the sixth leading cause of death.
The disease currently affects some 5.7 million people in the U.S. This figure is expected to rise to just under 14 million by 2050, by which time the annual costs of dementia will have nearly quadrupled from $277 billion to $1.1 trillion.
Nobody has yet discovered the root cause of Alzheimer's. However, increasing evidence suggests that it is complex and likely involves different biological processes, such as the buildup of toxic forms of tau and amyloid proteins in the brain.
The idea that microbes — and the way that the body defends against them — are involved in the development of Alzheimer's disease has been around for 60 years or more.
In particular, the study authors note that since the 1980s, "hundreds" of studies have reported associations between Alzheimer's disease and various microbes, including herpesviruses.
Need to clarify underlying viral mechanisms
However, beyond suggesting a link, none of those studies has shed much light on the underlying biology, and a "consistent association with specific viral species has not emerged."
A possible disease process involving viruses has been suggested by more recent research that showed how various types of microbe can "stimulate" the accumulation of amyloid-beta.
Toxic clumps of the protein have been found in the brains of people who had Alzheimer's when they died.
The new study started as a search for new Alzheimer's treatments in the vast repository of drugs that have already been approved for use in other diseases.
In order to do this, the teams had to create maps of the various genetic and biological networks of Alzheimer's disease so that they could compare them and how they might be affected by different drugs.
It was during this process that they discovered that Alzheimer's likely involves a complex mix of factors, including genetic features of the person with the disease and the viruses that they are exposed to during their lives.
Using data from a range of brain banks and cohort studies, the team took a step-by-step approach. They identified likely viral sequences with the help of information from the Mount Sinai Brain Bank. They then confirmed them using data from the Mayo Clinic Brain Bank, the Memory and Aging Project, and the Religious Orders Study.
By adding data from the Emory Alzheimer's Disease Research Center, the researchers gathered more clues on how the various viral sequences might alter protein levels in the brain.
After further analysis using advanced computer models, the team made several important findings. The first was that the herpesviruses HHV-6A and HHV-7 seemed to be more prevalent in samples from the brains of people with Alzheimer's disease.
Another important finding was the discovery of several "overlaps" between "virus-host interactions and genes associated with Alzheimer's risk."
The researchers also found evidence involving genes, transcription of genes, and proteins of several viruses influencing Alzheimer's disease biology.
"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 datasets that lends support to this line of inquiry."
Dr. Richard J. Hodes