Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition

Baglietto-Vargas, David, Kitazawa, Masashi, Le, Elaine J., Estrada-Hernandez, Tatiana, Rodriguez-Ortiz, Carlos J., Medeiros, Rodrigo, Green, Kim N. and LaFerla, Frank M. (2014) Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition. Neurobiology of Disease, 62 407-415. doi:10.1016/j.nbd.2013.10.019

Author Baglietto-Vargas, David
Kitazawa, Masashi
Le, Elaine J.
Estrada-Hernandez, Tatiana
Rodriguez-Ortiz, Carlos J.
Medeiros, Rodrigo
Green, Kim N.
LaFerla, Frank M.
Title Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition
Journal name Neurobiology of Disease   Check publisher's open access policy
ISSN 1095-953X
Publication date 2014-02-01
Sub-type Article (original research)
DOI 10.1016/j.nbd.2013.10.019
Open Access Status Not yet assessed
Volume 62
Start page 407
End page 415
Total pages 9
Place of publication Maryland Heights, MO United States
Publisher Academic Press
Language eng
Abstract Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg-AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models.
Keyword Alzheimer's disease
3xTg-AD mice
Neurofibrillary tangles
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Created: Tue, 06 Jun 2017, 10:40:41 EST by Kirstie Asmussen on behalf of Queensland Brain Institute