Congratulations to Bess Frost, PhD and the Frost Lab on their publication in Science Advances!
The paper is titled “Pathogenic tau–induced transposable element–derived dsRNA drives neuroinflammation” by Elizabeth Ochoa, Paulino Ramirez, Elias Gonzalez, Jasmine De Mange, William J. Ray, Kevin F. Bieniek, and Bess Frost. Dr. Frost is an Associate Professor with the Sam and Ann Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Disorders, and the Department of Cell Systems and Anatomy. She is the holder/manager of the Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders.
Abstract:
Deposition of tau protein aggregates in the brain of affected individuals is a defining feature of “tauopathies,” including Alzheimer’s disease. Studies of human brain tissue and various model systems of tauopathy report that toxic forms of tau negatively affect nuclear and genomic architecture, identifying pathogenic tau–induced heterochromatin decondensation and consequent retrotransposon activation as a causal mediator of neurodegeneration. On the basis of their similarity to retroviruses, retrotransposons drive neuroinflammation via toxic intermediates, including double-stranded RNA (dsRNA). We find that dsRNA and dsRNA sensing machinery are elevated in astrocytes of postmortem brain tissue from patients with Alzheimer’s disease and progressive supranuclear palsy and in brains of tau transgenic mice. Using a Drosophila model of tauopathy, we identify specific tau-induced retrotransposons that form dsRNA and find that pathogenic tau and heterochromatin decondensation causally drive dsRNA-mediated neurodegeneration and neuroinflammation. Our study suggests that pathogenic tau–induced heterochromatin decondensation and retrotransposon activation cause elevation of inflammatory, transposable element–derived dsRNA in the adult brain.
Science Advances. 6 Jan 2023. Vol 9, Issue 1. DOI: 10.1126/sciadv.abq5423