New evidence for viruses’ role in Alzheimer’s disease

Herpesvirus genes found in patients’ brains provide unprecedented evidence for a connection, but the viruses’ exact role remains unclear.

Results of a recent study breathe new life into an old hypothesis: that viruses, herpesviruses in particular, could play a role in Alzheimer's disease. Researchers analyzed DNA and RNA sequencing data from brain tissue donated by 622 people who had Alzheimer’s disease and 322 people who didn’t. They found that specific herpesviruses were more abundant in the brains of patients who had Alzheimer’s when they died. For two of the viruses, HHV-6A and HHV-7, the association with Alzheimer’s was particularly strong, even when compared to tissue samples of people with other neurodegenerative diseases.

The idea that viruses could somehow be involved in Alzheimer’s isn’t new. Previous studies have examined HSV-1, the virus that causes cold sores, but this evidence was less compelling. “Earlier studies focused on the presence of anti-HSV-1 antibodies, which meant that those with antibodies had encountered HSV-1 at some time during their lives. This new study showed HHV-6 and HHV-7 viral genes in the brains of Alzheimer’s disease patients at the time they died,” explains Sam Gandy, an Alzheimer’s disease specialist at the Ichan School of Medicine at Mount Sinai and one of the study’s senior authors.

The viruses were a surprise to the researchers who found them


The study’s authors hadn’t set out looking for viral genes. They’d originally hoped to find ways to repurpose existing drugs to treat Alzheimer’s. “We didn’t go looking for viruses, but viruses sort of screamed out at us,” said Ben Readhead, the study’s lead author. Surprised by what they’d found in the Mount Sinai Brain Bank samples, they turned to other brain banks to test additional samples. The same patterns were detected in samples from all the banks.

The researchers also modeled how the viruses’ genes interacted with human genes. “We were surprised to find that expression of a half dozen recognizable Alzheimer's genes was apparently modulated by HHV6/7,” said Gandy, “We tend to think of viral causes and genetic causes separately, but it is possible that viral proteins are acting as transcription factors that turn on Alzheimer’s disease genes.”

HHV-6A and HHV-7 aren’t unique to Alzheimer’s patients


The study does not suggest that Alzheimer’s disease is contagious. HHV-6A and HHV-7 are extremely common viruses. Nearly everyone above the age of six has at least one of them circulating in their blood. In most cases, the viruses are latent. "There are still a lot of unanswered questions around how we go from being able to detect it circulating in someone's blood to knowing whether it's active in a state that might be relevant to Alzheimer's disease," said Readhead.

The discovery raises as many questions as it answers


"While these findings do potentially open the door for new treatment options to explore in a disease where we've had hundreds of failed trials, they don't change anything that we know about the risk and susceptibility of Alzheimer's disease or our ability to treat it today," said Gandy.

Others in the Alzheimer’s research community are also cautious in their assessments of the study’s significance. David Reynolds, who was not involved in the study, is Chief Scientific Officer at Alzheimer’s Research UK. He points out that the part of the study involving actual human brain tissue does not provide any evidence for cause and effect. Still, Renyolds says the study is an important step forward: “This detailed analysis of human brain tissue takes this research further [than previous studies], indicating a relationship between the viruses and the activity of genes involved in Alzheimer’s, as well as brain changes, molecular signals, and symptoms associated with the disease. This was a well-conducted study, and the authors’ findings were supported by evidence drawn from three independent sources of donated brain tissue.”

Moving Alzheimer’s research forward


More research will be needed to determine why people with Alzheimer’s have more of these herpesviruses in their brains, and what role (if any) they play in the onset and progression of the disease. If scientists can solve these puzzles, they may uncover new ways to treat Alzheimer’s with antiviral medicines. Based on previous studies looking at HSV-1, clinical trials with the antiviral medicine Valtrex are already underway.

Beyond highlighting HHV-6A and HHV-7 as viruses of interest, the new study also demonstrates a promising path to progress in Alzheimer’s research. The researchers drew not only on samples and data from multiple brain banks, but also from cohort studies and raw genetic data. Richard Hodes, Director of the National Institute on Aging, which funded the study, said: “This research highlights the importance of sharing data freely and widely with the research community."