Alzheimer's disease has no cure and no well-understood cause. Experts know that tangles of tau protein that develop in the brain impact memory and function, but so far there is no solid research on a specific cause, a way to prevent it and, most importantly, a way to treat it.
Pfizer Pharmaceuticals ended all of their research into Alzheimer's in early 2018 due, in part, to the fact that none of the clinical trials for possible treatments had yielded any results. Another problem is the difficulty of examining brain tissue. Brain banks are needed to get samples of tissue, but the supply isn't always enough to meet the demand.
Recent research from the Icahn School of Medicine at Mount Sinai had to use three different brain banks to assemble enough samples to investigate the connection between the herpes virus and Alzheimer's. The work was a large meta-analysis to see if viruses impact gene expression and play a role in developing the disease. The idea that Alzheimer's could be related to virology and infections is controversial in neuroscience research, but with no reliable research studies that offer much hope, more avenues must be investigated if treatments are to be found.
Co-senior author and geneticist Joel Dudley is also a member of the ASU-Banner Neurodegenerative Disease Research Center. He explained, "The title of the talk that I usually give is, 'I Went Looking for Drug Targets and All I Found Were These Lousy Viruses.' We didn't set out to find what we found. Not even close. We were trying to find drugs that could be repurposed to treat Alzheimer's patients, but the patterns that emerged from our data-driven analysis all pointed towards these viral biology themes."
The study was a model of cooperation between different areas of research. The data from the three brain banks were coordinated through the National Institutes of Health's Accelerating Medicines Partnership—Alzheimer's Disease (AMP-AD) consortium. Access to this data gave the team large numbers of patients, including genomic data, RNA, DNA and proteins from multiple cohorts. Using algorithms and software they were able to create and map gene networks in the brain that are connected to Alzheimer's.
First author Ben Readhead explained how this collaboration made the project possible, stating, "This kind of analysis was only possible because the consortium had coordinated for all of these other groups to put their sequencing data in the AMP-AD Knowledge Portal in a pre-competitive environment that let us very quickly replicate our work across all these different cohorts. We needed access to sequences that are usually discarded in the course of studying the human genome. We needed to search for sequences from hundreds of different viruses, so having access to that raw, unprocessed data was absolutely key."
What the found after parsing such a huge amount of information was that DNA and RNA from the human herpesvirus were more abundant in the brains of patients who had an Alzheimer's diagnosis confirmed by post-mortem examination. There was also a correlation between higher levels of the viruses and dementia scores that revealed the severity of a patient's particular disease progression. The higher the viral load, the worse the cognitive scores tended to be.
In mapping out how genes from two specific viruses, HHV-6A and HHV-7, interacted with the genes involved in Alzheimer's, there was a connection between human genes and viral genes; the two sets of genes were regulating and being regulated in concert with each other.
The team stressed that their work did not show a causal effect between the virus and increase in the risk of getting Alzheimer's but the work was valuable because anything that points to the mechanics of the disease could eventually lead to effective treatments. According to the authors, the viral hypothesis in Alzheimer's disease is an area that cannot be "brushed away" in further research. Take a look at the video to learn more.
Sources: Journal, Neuron, Gizmodo National Institutes of Health
