Tau Activates Transposable Elements in Alzheimer's Disease

Cell Reports
Caiwei GuoJoshua M Shulman


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.


Dec 11, 1999·Brain Research·E AdamecR A Nixon
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brook BrouhaHaig H Kazazian
Aug 7, 2009·Nature·Nicole G CoufalFred H Gage
Jan 29, 2010·The New England Journal of Medicine·Henry W Querfurth, Frank M LaFerla
Nov 19, 2010·Nature·Alysson R MuotriFred H Gage
Aug 19, 2011·Nature Reviews. Genetics·Henry L Levin, John V Moran
Oct 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Patrick H MaxwellM Joan Curcio
Nov 1, 2011·Nature·J Kenneth BaillieGeoffrey J Faulkner
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicole G CoufalFred H Gage
Dec 21, 2011·Aging Cell·Vikram KhuranaM B Feany
Dec 30, 2011·Genome Biology·Prescott Deininger
Apr 6, 2013·Science·Paola N PerratScott Waddell
Jan 28, 2014·Nature Neuroscience·Bess FrostM B Feany
Jul 18, 2014·Neuron·Ram MadabhushiLi-Huei Tsai
Aug 19, 2014·Nature Neuroscience·Philip L De JagerDavid A Bennett
Apr 11, 2015·Cell·Kyle R UptonGeoffrey J Faulkner
May 21, 2015·Nature Reviews. Neuroscience·Frank L HeppnerBurkhard Becher
Jun 6, 2015·Mobile DNA·Weidong BaoOleksiy Kohany
Oct 2, 2015·Science Translational Medicine·Wenxue LiAvindra Nath
Nov 28, 2015·Nucleic Acids Research·Robert HubleyTravis J Wheeler
Mar 31, 2016·Nature Reviews. Immunology·George Kassiotis, Jonathan P Stoye
Sep 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jason G WoodStephen L Helfand
May 11, 2017·Acta Neuropathologica·Alifiya KapasiJulie A Schneider
Jun 24, 2017·Human Molecular Genetics·Mercedes PrudencioChristopher D Link
Sep 25, 2017·Biochemistry. Biokhimii︠a︡·M S ProtasovaT V Andreeva


Jun 6, 2018·Journal of Alzheimer's Disease : JAD·David A BennettJulie A Schneider
Aug 2, 2018·Acta Neuropathologica Communications·Mahmoud B MainaLouise C Serpell
Dec 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Roman SankowskiYousef Al-Abed
Nov 7, 2019·Genes·Seung Kyu Lee, Weidong Wang
Feb 6, 2020·Nature Reviews. Molecular Cell Biology·Weiqi ZhangJuan Carlos Izpisua Belmonte
Nov 24, 2019·BMC Bioinformatics·Federico AnsaloniRemo Sanges
May 20, 2020·Nucleic Acids Research·Huifang HuJing Qu
Feb 23, 2019·Journal of Experimental Neuroscience·Tassa K SaldiChristopher D Link
Sep 5, 2019·Frontiers in Neurology·Aurian SalehAlysson R Muotri
Nov 17, 2019·International Journal of Molecular Sciences·Denise DrongitisAldo Donizetti
Jan 11, 2020·Frontiers in Cell and Developmental Biology·Negin KhosravianiKarim Mekhail
Jun 21, 2020·Nature Communications·Kun-Yang LinHwei-Jan Hsu
Jul 14, 2018·Mobile DNA·Geoffrey J Faulkner, Victor Billon
Aug 11, 2018·Nature Reviews. Neurology·Charlotte Ridler
May 19, 2019·Acta Neuropathologica Communications·Niraj M ShanbhagLennart Mucke
Mar 27, 2019·Cold Spring Harbor Perspectives in Biology·Isabel LamVikram Khurana
Jan 21, 2021·Pharmaceuticals·Victoria GrögerHolger Cynis
Jan 25, 2021·Trends in Neurosciences·Michael P HantakJason D Shepherd
Oct 28, 2019·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Andrés A MoreraJacob C Schwartz
Sep 2, 2020·Annual Review of Medicine·William J Ray, Virginie Buggia-Prevot
Feb 22, 2021·Neuroscience Letters·Laura GilMaría E Jiménez-Capdeville
Nov 25, 2020·Seminars in Cell & Developmental Biology·Taylor A Evans, Jennifer Ann Erwin
Feb 18, 2021·Genome Biology and Evolution·Daniel K FabianJanet M Thornton
Apr 23, 2021·PLoS Genetics·Richard M KeeganJosh Dubnau
Apr 29, 2021·Cell Reports·Miguel PortilloDebra Toiber
Jun 5, 2021·Epigenetics & Chromatin·Xena Giada Pappalardo, Viviana Barra

Methods Mentioned

histone acetylation

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