Gene Therapy Tackles Tau Tangles in Mouse Models of Dementia

A study in the Proceedings of the National Academy of Sciences suggests a new method for helping the brain purge the toxic buildup of tau associated with dementia, reports FierceBiotech . Researchers discovered that an "oligomerized" subtype of the protein beta-arrestin-2 disrupts tau clearance in the brain, which when inactivated in mouse models of dementia caused pathogenic tau concentrations to significantly decline. Professor Stephen Liggett at the University of South Florida Health Morsani College of Medicine said beta-arrestin-2 by itself is not harmful, but the "incidental interaction" between its oligomerized form and tau clearance seems to underpin tau accumulation. Oligomerized beta-arrestin-2 was found to hinder a "cargo" protein from targeting excess tau in the brain for clearance. Preventing beta-arrestin-2 from accruing into the oligomerized subtype suppressed the disease-inducing tau. "We also noted that decreasing beta-arrestin-2 by gene therapy had no apparent side effects, but such a reduction was enough to open the tau clearance mechanism to full throttle, erasing the tau tangles," Liggett said.