Our paper entitled “TauActivates Transposable Elements in Alzheimer’s Disease” has been published in Cell Reports! Congrats!
Tau Activates Transposable Elements in Alzheimer’s Disease
Cell Reports, Volume 23, Issue 10, p2874–2880, 5 June 2018
Caiwei Guo9, Hyun-Hwan Jeong9, Yi-Chen Hsieh, Hans-Ulrich Klein, David A. Bennett, Philip L. De Jager, Zhandong Liu, and Joshua M. Shulman*
Summary
Aging and neurodegenerative disease are characterized by genomic instability in neurons, including aberrant activation and mobilization of transposable elements (TEs). Integrating studies of human postmortem brain tissue and Drosophila melanogaster models, we investigate TE activation in association with Tau pathology in Alzheimer’s disease (AD). Leveraging RNA sequencing from 636 human brains, we discover differential expression for several retrotransposons in association with neurofibrillary tangle burden and highlight evidence for global TE transcriptional activation among the long interspersed nuclear element 1 and endogenous retrovirus clades. In addition, we detect Tau-associated, active chromatin signatures at multiple HERV-Fc1 genomic loci. To determine whether Tau is sufficient to induce TE activation, we profile retrotransposons in Drosophila expressing human wild-type or mutant Tau throughout the brain. We discover heterogeneous response profiles, including both age- and genotype-dependent activation of TE expression by Tau. Our results implicate TE activation and associated genomic instability in Tau-mediated AD mechanisms.
Keywords
MAPT, retrotransposon, Alzheimer’s disease, genomic instability, neurodegeneration, RNA sequencing, LINE1, Alu, ERV, chromatin