ITEM METADATA RECORD
Title: AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice
Authors: Jaworski, Tomasz ×
Dewachter, Ilse
Lechat, Benoit
Croes, Sophie
Termont, Annelies
Demedts, David
Borghgraef, Peter
Devijver, Herman
Filipkowski, Robert K
Kaczmarek, Leszek
Kügler, Sebastian
Van Leuven, Freddy #
Issue Date: 2009
Series Title: PloS one vol:4 issue:10
Article number: e7280
Abstract: In Alzheimer's disease tauopathy is considered secondary to amyloid, and the duality obscures their relation and the definition of their respective contributions.Transgenic mouse models do not resolve this problem conclusively, i.e. the relative hierarchy of amyloid and tau pathology depends on the actual model and the genes expressed or inactivated. Here, we approached the problem in non-transgenic models by intracerebral injection of adeno-associated viral vectors to express protein tau or amyloid precursor protein in the hippocampus in vivo. AAV-APP mutant caused neuronal accumulation of amyloid peptides, and eventually amyloid plaques at 6 months post-injection, but with only marginal hippocampal cell-death. In contrast, AAV-Tau, either wild-type or mutant P301L, provoked dramatic degeneration of pyramidal neurons in CA1/2 and cortex within weeks. Tau-mediated neurodegeneration proceeded without formation of large fibrillar tau-aggregates or tangles, but with increased expression of cell-cycle markers.We present novel AAV-based models, which demonstrate that protein tau mediates pyramidal neurodegeneration in vivo. The data firmly support the unifying hypothesis that post-mitotic neurons are forced to re-enter the cell-cycle in primary and secondary tauopathies, including Alzheimer's disease.
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Experimental Genetics and Transgenesis (-)
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
289_Jaworski_PLoSONE.pdf Published 10199KbAdobe PDFView/Open

 


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science