Congratulations to Bess Frost, PhD and the Frost Lab on their publication in Progress in Neurobiology!
The paper is titled “Pathogenic tau accelerates aging-associated activation of transposable elements in the mouse central nervous systems” by Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L. DeVos, Bradley Hyman, Gabriel Chiu, Ethan R. Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J. Ray, 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.
Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer’s disease and related “tauopathies,” and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class of retrotransposons is particularly enriched. We show that protein encoded by Intracisternal A-particle, a highly active mouse ERV, is elevated in brains of tau transgenic mice. Using two complementary approaches, we find that brains of tau transgenic mice contain increased DNA copy number of transposable elements, raising the possibility that these elements actively retrotranspose in the context of tauopathy. Taken together, our study lays the groundwork for future mechanistic studies focused on transposable element regulation in the aging mouse brain and in mouse models of tauopathy and provides support for ongoing therapeutic efforts targeting transposable element activation in patients with Alzheimer’s disease.
Progress in Neurobiology. Available online 17 October 2021. https://doi.org/10.1016/j.pneurobio.2021.102181.