Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/30297
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jaworski, Tomasz | - |
dc.contributor.author | DEWACHTER, Ilse | - |
dc.contributor.author | Lechat, Benoit | - |
dc.contributor.author | Croes, Sophie | - |
dc.contributor.author | Termont, Annelies | - |
dc.contributor.author | Demedts, David | - |
dc.contributor.author | Borghgraef, Peter | - |
dc.contributor.author | Devijver, Herman | - |
dc.contributor.author | Filipkowski, Robert K | - |
dc.contributor.author | Kaczmarek, Leszek | - |
dc.contributor.author | Kügler, Sebastian | - |
dc.contributor.author | Van Leuven, Fred | - |
dc.date.accessioned | 2020-01-13T11:18:44Z | - |
dc.date.available | 2020-01-13T11:18:44Z | - |
dc.date.issued | 2009 | - |
dc.date.submitted | 2020-01-09T11:46:45Z | - |
dc.identifier.citation | PloS one, 4 (10) (Art N° ARTN e7280) | - |
dc.identifier.uri | http://hdl.handle.net/1942/30297 | - |
dc.description.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. | - |
dc.description.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. | - |
dc.description.sponsorship | : The investigations were made possible by funding and support from the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO-Vlaanderen, www.fwo.be), the Instituut voor Wetenschap en Techniek (IWT, www.iwt.be), the EEC-6th and 7th Framework Programs, the Rooms-fund, the KULeuven-Research Fund (BOF) and KULeuven-Research&Development. These funders had no rule in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. | - |
dc.language.iso | en | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.rights | 2009 Jaworski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | - |
dc.subject.other | Neuroscience | - |
dc.subject.other | neurodegeneration | - |
dc.subject.other | mediates | - |
dc.subject.other | neurofibrillary | - |
dc.subject.other | mice | - |
dc.subject.other | re-entry | - |
dc.subject.other | wild-type | - |
dc.subject.other | pyramidal | - |
dc.subject.other | tangle | - |
dc.subject.other | aav-tau | - |
dc.subject.other | cell-cycle | - |
dc.title | AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 10 | - |
dc.identifier.volume | 4 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | associated data : https://figshare.com/articles/AAV_Tau_Mediates_Pyramidal_Neurodegeneration_by_Cell_Cycle_Re_Entry_without_Neurofibrillary_Tangle_Formation_in_Wild_Type_Mice/146350 | - |
local.publisher.place | 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | ARTN e7280 | - |
dc.source.type | Article | - |
dc.identifier.doi | 10.1371/journal.pone.0007280 | - |
dc.identifier.pmid | 19794916 | - |
dc.identifier.isi | 000270354200007 | - |
dc.identifier.eissn | 1932-6203 | - |
local.provider.type | PubMed | - |
local.uhasselt.uhpub | no | - |
item.fullcitation | 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, Fred (2009) AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice. In: PloS one, 4 (10) (Art N° ARTN e7280). | - |
item.fulltext | With Fulltext | - |
item.accessRights | Open Access | - |
item.contributor | Jaworski, Tomasz | - |
item.contributor | DEWACHTER, Ilse | - |
item.contributor | Lechat, Benoit | - |
item.contributor | Croes, Sophie | - |
item.contributor | Termont, Annelies | - |
item.contributor | Demedts, David | - |
item.contributor | Borghgraef, Peter | - |
item.contributor | Devijver, Herman | - |
item.contributor | Filipkowski, Robert K | - |
item.contributor | Kaczmarek, Leszek | - |
item.contributor | Kügler, Sebastian | - |
item.contributor | Van Leuven, Fred | - |
crisitem.journal.issn | 1932-6203 | - |
crisitem.journal.eissn | 1932-6203 | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Figure_S4.tif | Published version | 4.96 MB | TIFF | View/Open |
Figure_S7.tif | Published version | 1.45 MB | TIFF | View/Open |
Figure_S3.tif | Published version | 4.89 MB | TIFF | View/Open |
Figure_S8.tif | Published version | 5.12 MB | TIFF | View/Open |
Figure_S5.tif | Published version | 5.26 MB | TIFF | View/Open |
Figure_S6.tif | Published version | 4.73 MB | TIFF | View/Open |
Figure_S2.tif | Published version | 468.88 kB | TIFF | View/Open |
journal pone 0007280.PDF | Published version | 10.2 MB | Adobe PDF | View/Open |
Table_S2.pdf | Published version | 39.94 kB | Adobe PDF | View/Open |
Figure_S1.tif | Published version | 4.84 MB | TIFF | View/Open |
Table_S1.pdf | Published version | 80.37 kB | Adobe PDF | View/Open |
SCOPUSTM
Citations
48
checked on Sep 2, 2020
WEB OF SCIENCETM
Citations
66
checked on Oct 4, 2024
Page view(s)
38
checked on Sep 7, 2022
Download(s)
14
checked on Sep 7, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.