First-in-Rat Study of Human Alzheimer's Disease Tau Propagation

Molecular Neurobiology
Tomas SmolekNorbert Zilka

Abstract

One of the key features of misfolded tau in human neurodegenerative disorders is its propagation from one brain area into many others. In the last decade, in vivo tau spreading has been replicated in several mouse transgenic models expressing mutated human tau as well as in normal non-transgenic mice. In this study, we demonstrate for the first time that insoluble tau isolated from human AD brain induces full-blown neurofibrillary pathology in a sporadic rat model of tauopathy expressing non-mutated truncated tau protein. By using specific monoclonal antibodies, we were able to monitor the spreading of tau isolated from human brain directly in the rat hippocampus. We found that exogenous human AD tau was able to spread from the area of injection and induce tau pathology. Interestingly, solubilisation of insoluble AD tau completely abolished the capability of tau protein to induce and spread of neurofibrillary pathology in the rat brain. Our results show that exogenous tau is able to induce and drive neurofibrillary pathology in rat model for human tauopathy in a similar way as it was described in various mouse transgenic models. Rat tau spreading model has many advantages over mouse and other organisms including size and comple...Continue Reading

References

Oct 15, 1992·The Biochemical Journal·F AhmadS Taneja
Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S G Greenberg, P Davies
Jun 18, 2004·Journal of Alzheimer's Disease : JAD·Valentina EcheverriaA Claudio Cuello
Oct 27, 2004·Molecular Medicine·Nelson Ruiz-OpazoVictoria Lm Herrera
May 18, 2007·Biochemical and Biophysical Research Communications·Ronnie FolkessonEirikur Benedikz
Dec 7, 2007·Neurobiology of Aging·Dorothy G FloodDavid S Howland
Jun 9, 2009·Nature Cell Biology·Florence ClavagueraMarkus Tolnay
Jan 26, 2010·Neurobiology of Aging·P KorhonenH Soininen
Jan 12, 2011·Annual Review of Physical Chemistry·Jeremy L England, Gilad Haran
Jun 10, 2011·Journal of the Royal Society, Interface·Craig J Thalhauser, Natalia L Komarova
Feb 9, 2012·PloS One·Li LiuKaren Duff
Mar 1, 2012·Neuron·Alix de CalignonBradley T Hyman
Mar 31, 2012·The Journal of Biological Chemistry·Najla KfouryMarc I Diamond
Apr 11, 2012·Journal of Neuropathology and Experimental Neurology·Peter T NelsonThomas G Beach
Jun 7, 2012·Neurobiology of Disease·Xiyun ChaiMartin Citron
Jul 24, 2012·Biochemical Society Transactions·Norbert ZilkaMichal Novák
Sep 15, 2012·Journal of Alzheimer's Disease : JAD·Stefanie K ForestPeter Davies
Oct 11, 2012·Scientific Reports·Cristian A Lasagna-ReevesRakez Kayed
Jan 18, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michiyo IbaVirginia M-Y Lee
May 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Florence ClavagueraMarkus Tolnay
Aug 21, 2013·Journal of Alzheimer's Disease : JAD·Lenka LevarskaMichal Novak
Nov 14, 2014·Journal of Neurochemistry·Sophie SokolowKaren H Gylys
Nov 20, 2014·The Journal of Biological Chemistry·Benjamin FalconSuchira Bose
Mar 11, 2015·Frontiers in Cellular Neuroscience·Santosh JadhavNorbert Zilka
May 20, 2015·Cell Reports·Sara CalafateDiederik Moechars
Jan 23, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Samuel J JacksonSuchira Bose
Oct 19, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Wen HuKhalid Iqbal
May 14, 2016·Science Translational Medicine·Matthew R BrierBeau M Ances
Nov 5, 2016·The Journal of Experimental Medicine·Jing L GuoVirginia M Y Lee

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Citations

Jan 11, 2020·Frontiers in Aging Neuroscience·Tomas SmolekSantosh Jadhav
May 21, 2019·Frontiers in Molecular Neuroscience·Eftychia VasiliTiago Fleming Outeiro
Oct 23, 2019·Frontiers in Aging Neuroscience·Ena ŠpanićGoran Šimić
Nov 19, 2019·Biological Psychiatry·Thomas VogelsMichael Schöll
Jul 3, 2021·International Journal of Molecular Sciences·Aiko RobertThomas Vogels

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Methods Mentioned

BETA
transgenic

Software Mentioned

AIDA Biopackage Image Data Analyzer
Graph Pad Prism
GraphPad

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