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Transposable element activation in Alzheimer's disease and related tauopathies
Transposable elements, known colloquially as ‘jumping genes’, constitute approximately 45% of the human genome. Cells utilize epigenetic defenses to limit transposable element jumping, including formation of silencing heterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate clearance of transposable element transcripts. We have utilized fruit flies, mice and postmortem human brain samples to identify transposable element dysregulation as a key mediator of neuronal death in tauopathies, a group of neurodegenerative disorders that are pathologically characterized by deposits of tau protein in the brain. Mechanistically, we find that heterochromatin decondensation and reduction of piwi and piRNAs drive transposable element dysregulation in tauopathy. We further report a significant increase in transcripts of the endogenous retrovirus class of transposable elements in human Alzheimer’s disease and progressive supranuclear palsy, suggesting that transposable element dysregulation is conserved in human tauopathy. Taken together, our data identify heterochromatin decondensation, piwi and piRNA depletion and consequent transposable element dysregulation as a pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.

Oct 1, 2020 04:00 PM in London

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Bess Frost
Dr @Barshop Institute for Longevity and Aging Studies
Dr. Bess Frost is an Associate Professor at the Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Disease, and the department of Cell Systems and Anatomy at the University of Texas Health San Antonio. Dr. Frost has been a member of the Tau Consortium since 2017. Designated as a “Rising STAR” in the University of Texas system, Dr. Frost was the recipient of a 2019 Presidential Excellence Award for Junior Research Scholar from the University of Texas Health San Antonio, and a 2020 O’Donnell Award in Medicine from the Academy of Medicine, Engineering, and Science of Texas.