Mild traumatic brain injury (TBI) may reactivate latent herpes simplex virus type 1 (HSV-1) in the brain and contribute to neurodegeneration and development of Alzheimer’s disease (AD) pathology, a new study suggested.
Using a three-dimensional (3D) human brain tissue model, researchers observed that quiescent HSV-1 can be reactivated by a mechanical jolt mimicking concussion, leading to signature markers of AD, including neuroinflammation and production of amyloid beta and phosphorylated tau (p-tau) and gliosis — a phenotype made worse by repeated head injury.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks and lower the risk of Alzheimer’s disease,” lead investigator Dana Cairns, PhD, with the Department of Biomedical Engineering at Tufts University, Medford, Massachusetts, said in a statement.
But outside experts urged caution in drawing any firm conclusions, pending further study.
The study was published online on January 7 in the journal Science Signaling.
HSV-1 a Major AD Risk Factor?
TBI is a major risk factor for AD and dementia, but the pathways in the brain leading from TBI to dementia are unknown.
HSV-1 is found in over 80% of people; varicella zoster virus (VZV) is found in about 95%. Both viruses are known to enter the brain and lay dormant in neurons and glial cells. Prior evidence indicates that HSV-1 in the brain of APOE-ε4 carriers confers a strong risk for AD.
A number of years ago, the team created a 3D model of human brain tissue to study the link between TBI, the viruses, and dementia. The model is 6 mm wide, shaped like a donut, and made of a spongy material of silk protein and collagen saturated with neural stem cells. The cells mature into neurons, communicate with each other, and form a network that mimics the brain environment.
In an earlier study using the model quiescently infected with HSV-1, Cairns and colleagues found that subsequent exposure to VZV created the inflamm