Active glycogen synthase kinase-3 and tau pathology-related tyrosine phosphorylation in pR5 human tau transgenic mice

Koehler, Christoph, Dinekov, Maja and Goetz, Juergen (2013) Active glycogen synthase kinase-3 and tau pathology-related tyrosine phosphorylation in pR5 human tau transgenic mice. Neurobiology of Aging, 34 5: 1369-1379. doi:10.1016/j.neurobiolaging.2012.11.010


Author Koehler, Christoph
Dinekov, Maja
Goetz, Juergen
Title Active glycogen synthase kinase-3 and tau pathology-related tyrosine phosphorylation in pR5 human tau transgenic mice
Journal name Neurobiology of Aging   Check publisher's open access policy
ISSN 0197-4580
1558-1497
Publication date 2013-05
Sub-type Article (original research)
DOI 10.1016/j.neurobiolaging.2012.11.010
Volume 34
Issue 5
Start page 1369
End page 1379
Total pages 11
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2014
Language eng
Formatted abstract
We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/ Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. These neurons were rare in 8.5-month-old, but numerous in 18.5- and 28-month-old pR5 mice. Two antibodies that detect phosphotyrosine residues more generally only stained these neurons. In contrast, we did not find increased phosphotyrosine in neuronal perikarya of mice with an amyloid-b plaque pathology. Our results suggest a link between increased tyrosine phosphorylation and tau aggregation. They also reveal for the mouse models studied, that tau- rather than an amyloid-β peptide-induced pathology is associated with increased neuronal tyrosine phosphorylation.
Keyword Alzheimer's disease
At100
Fyn
Phosphotyrosine
Pyk2
Tauopathy
Accompanies Disease Progression
Alzheimers-Disease
P301L Tau
Granulovacuolar Degeneration
Neurofibrillary Tangles
A-Beta
Amyloid Plaques
Mouse Models
Rat-Brain
In-Vivo
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 4 January 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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