Amyloid beta protein protects brain from herpes infection by entrapping viral particles

July 5, 2018, Massachusetts General Hospital
Credit: CC0 Public Domain

A Massachusetts General Hospital (MGH) study has found the mechanism by which amyloid beta (A-beta) - the protein deposited into plaques in the brains of patients with Alzheimer's disease—protects from the effects of herpes viruses commonly found in the brain. Along with another study appearing in the same July 11 issue of Neuron, which found elevated levels of three types of herpes viruses in the brains of patients with Alzheimer's disease, the MGH team's results support a potential role for viral infection in accelerating A-beta deposition and Alzheimer's progression.

"There have been multiple epidemiological studies suggesting people with infections are at higher risk for Alzheimer's disease, along with the most recent findings from Icahn School of Medicine at Mt. Sinai that are being published with our study," says Rudolph Tanzi, Ph.D., director of the Genetics and Aging Research Unit in the MassGeneral Institute for Neurodegenerative Disease (MIND) and co-corresponding author of the Neuron paper. "Our findings reveal a simple and direct mechanism by which herpes infections trigger the deposition of amyloid as a defense response in the brain. In this way, we have merged the hypothesis and amyloid hypothesis into one 'Antimicrobial Response Hypothesis' of Alzheimer's disease."

Previous studies led by Tanzi and co-corresponding author Robert Moir, Ph.D., also of the MIND Genetics and Aging Research Unit, found evidence indicating that A-beta—long thought to be useless "metabolic garbage—was an antimicrobial protein of the body's innate immune system, capable of protecting animal models and cultured human brain cells from dangerous infections. Given that brain infection with herpes simplex—the virus that causes cold sores—is known to increase with aging, leading to almost universal presence of that and other herpes strains in the brain by adulthood, the MGH team set out to find whether A-beta could protect against and, if so, the mechanism by which such protection takes place.

After first finding that transgenic mice engineered to express human A-beta survive significantly longer after injections of herpes simplex into their brains than do nontransgenic mice, the researchers found that A-beta inhibited infection of cultured human brain cells with herpes simplex and two other herpes strains by binding to proteins on the viral membranes and clumping into fibrils that entrap the virus and prevent it from entering cells. Further experiments with the transgenic mice revealed that introduction of herpes simplex into the brains of 5- to 6-week-old animals induced rapid development of A-beta plaques, which usually appear only when the animals are 10 to 12 weeks old.

"Our findings show that amyloid entrapment of herpes viruses provides immediate, effective protection from infection," says Moir. "But it's possible that chronic infection with pathogens like herpes that remain present throughout life could lead to sustained and damaging activation of the amyloid-based immune response, triggering the brain inflammation that drives a cascade of pathologies leading to the onset of Alzheimer's disease. A key insight is that it's not direct killing of brain cells by herpes that causes Alzheimer's, rather it's the immune response to the virus that leads to brain-damaging neuroinflammation."

He continues, "Our data and the Mt. Sinai findings suggest that an antimicrobial protection model utilizing both anti-herpes and anti-amyloid drugs, could be effective against early Alzheimer's disease. Later on when neuroinflammation has begun, greater benefit may come from targeting inflammatory molecules. However, it remains unclear whether infection is the disease's root cause. After all, Alzheimer's is a highly heterogeneous disease, so multiple factors may be involved in its development.

Tanzi says, "We are currently conducting what we call the 'Brain Microbiome Project,' to characterize the population of microbes normally found in the brain. The brain used to be considered sterile but it turns out to have a resident population of microbes, some of which may be needed for normal brain health. Our preliminary findings suggest that the brain microbiome is severely disturbed in Alzheimer's disease and that bad players—including herpes viruses—seem to take advantage of the situation, leading to trouble for the patient. We are exploring whether Alzheimer's pathogenesis parallels the disrupted microbiome models seen in conditions like inflammatory bowel disease, and the data generated to date are both surprising and fascinating."

Explore further: Using herpes drugs to slow down Alzheimer's disease could become reality

More information: Neuron (2018). DOI: 10.1016/j.neuron.2018.06.030

Related Stories

Using herpes drugs to slow down Alzheimer's disease could become reality

December 13, 2016
The first clinical study to investigate if herpes virus drugs can have an effect on fundamental Alzheimer's disease processes has been launched at Umeå University in Sweden. The research group has previously demonstrated ...

Human amyloid-beta acts as natural antibiotic in the brains of animal models

May 25, 2016
A new study from Massachusetts General Hospital (MGH) investigators provides additional evidence that amyloid-beta protein - which is deposited in the form of beta-amyloid plaques in the brains of patients with Alzheimer's ...

Can nanotechnology help treat Alzheimer's?

June 19, 2018
Alzheimer's disease (AD) is the most common form of dementia. It takes a devastating toll on patients and family members, who are usually the caregivers. Current drugs only treat symptoms of AD, not its causes.

Cold sores increase the risk of dementia

October 20, 2014
Infection with herpes simplex virus increases the risk of Alzheimer's disease. Researchers at Umeå University, Sweden, claim this in two studies in the journal Alzheimer's & Dementia.

Preclinical evaluation of a vaccine against herpes viruses

August 4, 2016
Oral and genital herpes are caused by the herpes simplex virus type 1 (HSV-1) and the herpes simplex virus type 2 (HSV-2), which both cause lifelong infection. HSV-2 infection is associated with increased risk for HIV infection. ...

Brain cholesterol associated with increased risk of Alzheimer's disease

May 7, 2018
Researchers have shown how cholesterol—a molecule normally linked with cardiovascular diseases—may also play an important role in the onset and progression of Alzheimer's disease.

Recommended for you

Wiring diagram of the brain provides a clearer picture of brain scan data

December 14, 2018
Already affecting more than five million Americans older than 65, Alzheimer's disease is on the rise and expected to impact more than 13 million people by 2050. Over the last three decades, researchers have relied on neuroimaging—brain ...

Scientists identify method to study resilience to pain

December 14, 2018
Scientists at the Yale School of Medicine and Veterans Affairs Connecticut Healthcare System have successfully demonstrated that it is possible to pinpoint genes that contribute to inter-individual differences in pain.

Parents' brain activity 'echoes' their infant's brain activity when they play together

December 13, 2018
When infants are playing with objects, their early attempts to pay attention to things are accompanied by bursts of high-frequency activity in their brain. But what happens when parents play together with them? New research, ...

In the developing brain, scientists find roots of neuropsychiatric diseases

December 13, 2018
The most comprehensive genomic analysis of the human brain ever undertaken has revealed new insights into the changes it undergoes through development, how it varies among individuals, and the roots of neuropsychiatric illnesses ...

Researchers find the cause of and cure for brain injury associated with gut condition

December 13, 2018
Using a mouse model of necrotizing enterocolitis (NEC)—a potentially fatal condition that causes a premature infant's gut to suddenly die—researchers at Johns Hopkins say they have uncovered the molecular causes of the ...

Researchers discover abundant source for neuronal cells

December 13, 2018
USC researchers seeking a way to study genetic activity associated with psychiatric disorders have discovered an abundant source of human cells—the nose.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.