A team of scientists and engineers at Tufts University used a 3D human tissue culture model to find a possible causal relationship between herpes simplex virus and sporadic Alzheimer's disease, according to a recent study published in the journal Science Advances.
3D brain-like tissue model linked herpes to Alzheimer's
Specifically, the team found a possible link between the herpes simplex virus I infection (HSV-1) and Alzheimer's disease. The new model will open the door for further studies into causes and possible treatments of the neurodegenerative condition, reports MedicalXpress.
Once the researchers infected neurons in a bioengineered brain model with HSV-1, they saw the formation of amyloid plaques, neuroinflammation, neuronal loss, and diminished neural network functionality — all normal features of a patient suffering from Alzheimer's disease. Treatment of the 3D brain tissue models with the antiviral drug valacyclovir seemed to reduce plaque formation and other common markers of the disease.
Previous studies by other researchers have seen pathogens as environmental agents potentially responsible for the occurrence of Alzheimer's disease, with several studies signifying HSV-1.
The 3D brain-like tissue model is a 6-millimeter-wide, donut-shaped, and sponge-like material composed of silk protein and collagen. It's populated with nominal neural stem cells the researchers guided to transform into neurons.
"Our brain tissue model allowed us to take a closer look at the potential causal relationship between herpes and Alzheimer's disease, and the results were intri[g]uing," said David Kaplan, Stern Family Professor of Engineering. "After just 3 days of herpes infection, we saw large and dense plaque formations of beta amyloid protein, as well as increased expression of some of the enzymes responsible for generating the plaques. We observed neuron loss, neuroinflammation and depressed signaling between neurons — everything we observe in patients. Never before have so many facets of the disease been replicated in vitro."
Alzheimer's, gene expression, and HSV-1 brain tissue
The researchers found 40 Alzheimer's-related genes over-expressed in the HSV-1 infected 3D brain tissue, compared to non-infectious tissue. Gene coding for the enzymes cathepsin G and BACE2 were prominent — both typically associated with Alzheimer's disease and involved in the production of beta-amyloid peptides present in plaques. Some over-expressed gene products seen in the study's tissue model might one day become drug candidates, reports MedicalXpress.
"This is a model of Alzheimer's disease which is very different from what other studies have used," said Dana Cairns, first author of the study and a postdoctoral research candidate in David Kaplan's lab. "Most other studies relied on using genetic mutations in the neurons to induce Alzheimer's disease-like phenotypes and ours does not, which is what really sets it apart. Our model using normal neurons allows us to show that herpes alone is sufficient to induce Alzheimer's disease phenotypes."