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Tau Activates Transposable Elements in Alzheimer's Disease.
Guo, Caiwei; Jeong, Hyun-Hwan; Hsieh, Yi-Chen; Klein, Hans-Ulrich; Bennett, David A; De Jager, Philip L; Liu, Zhandong; Shulman, Joshua M.
Afiliación
  • Guo C; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
  • Jeong HH; Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Hsieh YC; Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Klein HU; Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA; Cell Circuits Program, Broad Institute, Cambridge, MA 02142, USA.
  • Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
  • De Jager PL; Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA; Cell Circuits Program, Broad Institute, Cambridge, MA 02142, USA.
  • Liu Z; Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Shulman JM; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurology
Cell Rep ; 23(10): 2874-2880, 2018 06 05.
Article en En | MEDLINE | ID: mdl-29874575
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Elementos Transponibles de ADN / Proteínas tau / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Elementos Transponibles de ADN / Proteínas tau / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos