Growing evidence implicates herpes viruses in Alzheimer's

The Alzheimer's study

The research team — from Mount Sinai and the Arizona State University-Banner Neurodegenerative Disease Research Center — examined data from 622 brain donors with late-onset Alzheimer's disease (AD) and 322 without the disease, and sequenced their exome DNA to see each person's inherited genes.

• They also looked at clinical assessments of the patient taken before they died to see the trajectory of their cognitive decline and pathology assessments after they died to check the severity of plaques and tangles.

"The data sets we used in the study are some of the first data sets where we had deep genomic sequencing of tissue collected directly from affected brains, which enabled an entirely new opportunity to look for viral sequences," study author Joel Dudley tells Axios.

What they found: Two strains of herpes virus were prevalent and active in the brains of people with Alzheimer's — human herpes virus (HHV) 6A and 7, which are found inactive in most people due to childhood infections like roseola.

• However, these dormant viruses can "wake up" and cause tissue damage and cell death, says the University of South Florida College of Medicine's Peter Medveczky, who was not part of this study.
• One train of thought is that "there are 5 of 6 genes linked to Alzheimer's. It may be that the protein from these viruses can act as transcription factors and cause the expression of those genes," explains Sam Gandy, study author and Alzheimer's disease specialist at Icahn School of Medicine at Mount Sinai.

The issue: Many people have HHV 6A and 7 in their system, but not all get Alzheimer's, says Anthony Komaroff, a Harvard Medical School professor and senior physician at Brigham and Women’s Hospital who was not part of this study.

"This study makes a link to AD more plausible (but still far from proven) by showing that there is more virus in the brains of patients with AD, that the virus is active (making proteins), and that those proteins interact with human genes that have previously been linked to AD."

Potential impact: This could change the targets for Alzheimer's drugs, several scientists said. As NPR points out, one possibility is to give antiviral drugs to people with high levels of herpes virus in their brains. The other is to try to prevent the brain's immune system from reacting to the virus in a way that accelerates AD.

"This work will undoubtedly stimulate novel medical interventions to inhibit activity of these viruses in patients with mild or pre-Alzheimer’s disease."

What's next: Dudley says they're seeking funding for studies on living people to better understand how the virus gets into brain tissues. Some believe they are carried via white blood cells, whereas others say it may enter through the olfactory nerve traveling from the nose to the brain.

The role of viruses in other diseases

The complex relationship between human genes and the factors that affect them, including environment, bacteria and viruses, is becoming clearer.

• "Viruses and bacteria have been shown to cause several kinds of cancer, like cancer of the stomach, liver, cervix, and lymph glands (lymphoma)," Komaroff says.
• For example, Epstein-Barr virus may play a role in various autoimmune disorders, like lupus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease, although Komaroff points out this is not yet proven.
• "There is some evidence that viruses may play a role in causing diseases of the hormone (endocrine) system, and even in atherosclerosis (the biggest killer of people in the developed nations)," Komaroff says.

Go deeper: The Mount Sinai research team made a video about their findings.