Title: Lentiviral Delivery of the Human Wild-type Tau Protein Mediates a Slow and Progressive Neurodegenerative Tau Pathology in the Rat Brain
Authors: Caillierez, Raphaëlle ×
Bégard, Séverine
Lécolle, Katia
Deramecourt, Vincent
Zommer, Nadège
Dujardin, Simon
Loyens, Anne
Dufour, Noëlle
Aurégan, Gwennaëlle
Winderickx, Joris
Hantraye, Philippe
Déglon, Nicole
Buée, Luc
Colin, Morvane #
Issue Date: Jul-2013
Publisher: Academic Press
Series Title: Molecular Therapy vol:21 issue:7 pages:1358-68
Article number: 10.1038/mt.2013.66
Abstract: Most models for tauopathy use a mutated form of the Tau gene, MAPT, that is found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and that leads to rapid neurofibrillary degeneration (NFD). Use of a wild-type (WT) form of human Tau protein to model the aggregation and associated neurodegenerative processes of Tau in the mouse brain has thus far been unsuccessful. In the present study, we generated an original "sporadic tauopathy-like" model in the rat hippocampus, encoding six Tau isoforms as found in humans, using lentiviral vectors (LVs) for the delivery of a human WT Tau. The overexpression of human WT Tau in pyramidal neurons resulted in NFD, the morphological characteristics and kinetics of which reflected the slow and sporadic neurodegenerative processes observed in sporadic tauopathies, unlike the rapid neurodegenerative processes leading to cell death and ghost tangles triggered by the FTDP-17 mutant Tau P301L. This new model highlights differences in the molecular and cellular mechanisms underlying the pathological processes induced by WT and mutant Tau and suggests that preference should be given to animal models using WT Tau in the quest to understand sporadic tauopathies.Molecular Therapy (2013); doi:10.1038/mt.2013.66.
ISSN: 1525-0016
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Physiology of Plants and Micro-organisms Section - miscellaneous
× corresponding author
# (joint) last author

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