Viral Vector

Emerging Evidence That Microbes Might Drive Alzheimer's Symptoms

A team of U.S. scientists made headlines last month when they published a study suggesting that infection with common strains of herpes virus acquired in childhood might play a role in the onset of Alzheimer's disease.

The findings, published in the journal Neuron, came as a validation of sorts for UNM's Elaine Bearer, MD, PhD, who is one of a small - but growing - number of researchers who believe chronic infections might lie at the root of Alzheimer's and other brain disorders.

"What this says is infections of childhood can lead to adult diseases of aging," said Bearer, the Harvey Family Professor in the Department of Pathology. "I'm really excited by it. They did something that no one else has yet done, which is brilliant."

In 2016, Bearer was one of an international group of researchers who published a paper in the Journal of Alzheimer's Disease that cited multiple lines of evidence dating back 60 years that the brains of Alzheimer's patients showed distinctive signs of microbial infection. The authors declared it was time for serious research into whether infectious agents play a role in Alzheimer's.

But raising the possibility that infections might give rise to Alzheimer's symptoms is controversial. For decades, researchers have tried to determine what causes a normally occurring protein called amyloid beta to form sticky plaques that spread throughout the brain and destroy tissue, eventually leading to the loss of memory and other functions.

While the destructive process is well documented, what triggers it remains a mystery. For some patients there is a clear genetic risk, and lifestyle and metabolic factors have also been identified. The puzzle helps explain why no effective drug to reverse Alzheimer's symptoms has been found, despite billions spent on research.

In the Neuron study, scientists at the Icahn School of Medicine at Mt. Sinai in New York, together with colleagues in Phoenix and Seattle, examined brain tissue from hundreds of people who had died from Alzheimer's for signs of viral infection. Two types of herpes viruses, known as HHV-6A and HHV-7, were closely associated with the characteristic damage caused by Alzheimer's.

Bearer notes that in babies and young children those viruses cause roseola, a short-lived infection characterized by high fever and rash. It usually doesn't cause serious complications and subsides quickly.

"These viruses have been thought to be nuisances," she says. Because roseola typically is self-limiting, "we haven't paid any attention to whether the virus is still there in adulthood and causing damage."

The roseola-causing strains of herpes belong to a family of related viruses, including herpes simplex (which can cause orolabial and genital herpes), varicella zoster (which causes chickenpox and shingles), Epstein-Barr virus (the cause of mononucleosis) and cytomegalovirus. Nearly all adults have been infected with at least one of these viruses.

It's well documented that herpes viruses can linger for decades in the peripheral nervous system, long after the immune system has cleared an infection. Bearer and others believe that in adulthood these viruses may reactivate and invade the brain.

Scientists theorize that the amyloid beta plaques characteristic of Alzheimer's actually represent the brain's attempt to protect itself from these microbes, Bearer says. "Amyloid beta protein is a component of innate immunity," she says. "What it's trying to do is create a cage around the pathogen so the pathogen can't work."

The possibility that infections might play a role in triggering Alzheimer's raises the prospect that a vaccine could perhaps be developed to prevent them. Bearer says a number of companies have tried to create vaccines to block herpes viruses without success.

While the new paper zeroes in on two likely candidates, it's clear that many other types of microorganisms can find their way into brain tissue, Bearer says. "What we've been advocating is we need to know all the pathogens that create an inflammatory response in the brain."