New Study Links Antiviral Response to Alzheimer’s Development

Research from Mass General Brigham has uncovered a potential link between the brain’s antiviral defense mechanisms and the development of Alzheimer’s disease. The study, published in Nature Neuroscience, reveals that hyperphosphorylation of the protein known as phospho-tau (p-tau) may result from the brain’s response to viral infections, particularly the HSV1 virus.

During the study, researchers investigated how tau proteins interact with neurons when exposed to the HSV1 virus. They found that the infection led to an increase in hyperphosphorylated tau, which subsequently formed aggregates resembling the tangles associated with Alzheimer’s disease. This suggests that the very processes contributing to Alzheimer’s may also have evolved as protective responses against infections.

Rudolph Tanzi, Ph.D., a senior author and Director of the McCance Center for Brain Health at Mass General Brigham, discussed the evolutionary implications of these findings. “Many features of Alzheimer’s disease, which we view as pathological today, may have once served a protective function,” he stated. Tanzi posits that individuals carrying genes predisposing them to Alzheimer’s may have had a survival advantage when human life expectancy was significantly shorter.

The study highlights a dual role for tau proteins: while they may contribute to disease pathology, they also act as an antiviral defense mechanism. The researchers demonstrated that tau could bind to the capsid of the HSV1 virus, effectively neutralizing its infectivity and preventing further damage to neurons.

In their experiments, the team utilized a human-derived neuron cell culture model that was sensitive to phosphorylated tau. Upon exposure to the HSV1 virus, they observed that infected neurons released hyperphosphorylated tau, which then bound to the virus, creating a feedback loop that limited viral spread.

Lead author William Eimer, Ph.D., emphasized the significance of their results: “Our findings reveal an important novel role for tau as an antiviral protein against HSV1 and probably other viruses.” This discovery adds a new layer of complexity to our understanding of Alzheimer’s disease and suggests that the characteristics we associate with the illness may not solely be detrimental.

The implications of this research extend beyond just Alzheimer’s. As Tanzi noted, the evolution of such a response highlights the intricate balance between survival mechanisms and disease pathology as human lifespans have increased. While these genetic predispositions may have once offered protection against infections, they could now contribute to the rising prevalence of neurodegenerative diseases.

As research continues, understanding the interplay between viral infections and neurodegenerative disorders like Alzheimer’s could pave the way for new therapeutic strategies that target these underlying mechanisms. The findings underscore the importance of ongoing investigation into the multifaceted nature of brain health and disease.