Universität zu Köln

Koehler, Christoph, Fuhr, Vivien and Dinekov, Maja (2017). Distribution of spleen tyrosine kinase and tau phosphorylated at tyrosine 18 in a mouse model of tauopathy and in the human hippocampus. Brain Res., 1677. S. 1 - 14. AMSTERDAM: ELSEVIER. ISSN 1872-6240

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Abstract

Purpose: Spleen tyrosine kinase (Syk) has been shown to phosphorylate tyrosine 18 of tau in vitro. It has been proposed that increased immunoreactivity for double-phosphorylated Syk in hippocampal neurons of Alzheimer's disease cases indicates a not yet defined neurodegenerative process. To investigate this possibility we have studied Syk and tau phosphorylated at tyrosine 18 (pTyr18) in transgenic mice and human hippocampi. Methods: We performed immunohistochemistry, immunofluorescence labeling and Western blotting and compared the distribution of Syk double-phosphorylated at tyrosines 525 and 526 and pTyr18 in human tau transgenic pR5 mice and human hippocampi with low and high Braak stages for neurofibrillary tangle pathology. Results: pTyr18 appeared early during the course of neurodegeneration in pR5 mice and was widely distributed in the pR5 brain, including neuronal somata and fiber tracts. In contrast, only strongly pTyr18- and AT100-(tau phosphorylated at Thr212 and Ser214) positive neurons with a fibrillary tau pathology in old pR5 mice and microglia displayed immunoreactivity for double-phosphorylated Syk. In human hippocampi, phosphorylated Syk was mainly present in granulovacuolar inclusions in hippocampal pyramidal neurons and did not co-locate with pTyr18 in these neurons. We observed pTyr18-positive neurons and neurons with granular pSyk immunoreactivity already at early Braak stages and their number was markedly increased in Braak stage VI. Conclusion: Syk appears unlikely to be the major kinase that phosphorylates tyrosine 18 of tau in tauopathy. It possibly phosphorylates tyrosine 18 of tau and regulates other tau kinases in neurons with a fibrillary tau pathology. (C) 2017 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Koehler, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Vivien UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinekov, Maja UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-207864
DOI:	10.1016/j.brainres.2017.08.029
Journal or Publication Title:	Brain Res.
Volume:	1677
Page Range:	S. 1 - 14
Date:	2017
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1872-6240
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACCOMPANIES DISEASE PROGRESSION; GRANULOVACUOLAR DEGENERATION; ALZHEIMERS-DISEASE; STRESS GRANULES; SYK EXPRESSION; PROTEIN-TAU; C-ABL; FYN; DOMAINS; CORTEX Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20786