Hyperphosphorylated tau, the protein that makes up the tangles observed in tauopathies like Alzheimer’s disease, may be the consequence of an antiviral mechanism intended to protect the brain from infections. That’s according to new research analyzing tau’s microbial activity against herpes simplex virus 1 (HSV1) performed by scientists at Mass General Brigham (Mass Gen) and their collaborators at Harvard University and elsewhere. Full details are provided in a new Nature Neuroscience paper titled “Phosphorylated tau exhibits antimicrobial activity capable of neutralizing herpes simplex virus 1 infectivity in human neurons.” The findings support an idea that Rudolph Tanzi, PhD, the paper’s senior author and director of the McCance Center for Brain Health and Genetics and Aging Research Unit in the neurology department at Mass Gen, and his colleagues have been interested in studying. That idea being that people with genes that predispose them to Alzheimer’s pathology may once have had a survival advantage against widespread infection when humans lived for 30 years or less. But as lifespan increased, those once protective mutations increased susceptibility to Alzheimer’s. Considering the findings from this research alongside the group’s earlier work showing that “amyloid beta, the main component of senile plaques, is an antimicrobial protein, we believe Alzheimer’s pathology may have evolved as an orchestrated host defense system for the brain,” Tanzi said. Specifically, “our data suggest that the ‘pathogenic’ characteristics of tau hyperphosphorylation, microtubule destabilization, and aggregation are part of an antiviral response, in which tau serves as a host defense protein in the innate immune system of the brain,” the scientists wrote. “The combined antimicrobial activities of Aβ…
