title: Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain.
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.
authors.affiliation: Inserm, UMR837, Lille, France.
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Caillierez
authors.forename: Séverine
authors.initials: S
authors.lastname: Bégard
authors.forename: Katia
authors.initials: K
authors.lastname: Lécolle
authors.forename: Vincent
authors.initials: V
authors.lastname: Deramecourt
authors.forename: Nadège
authors.initials: N
authors.lastname: Zommer
authors.forename: Simon
authors.initials: S
authors.lastname: Dujardin
authors.forename: Anne
authors.initials: A
authors.lastname: Loyens
authors.forename: Noëlle
authors.initials: N
authors.lastname: Dufour
authors.forename: Gwennaëlle
authors.initials: G
authors.lastname: Aurégan
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.forename: Nicole
authors.initials: N
authors.lastname: Déglon
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: Morvane
authors.initials: M
authors.lastname: Colin
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins