Universität zu Köln

Koehler, Christoph, Dinekov, Maja and Goetz, Juergen (2014). Granulovacuolar degeneration and unfolded protein response in mouse models of tauopathy and A beta amyloidosis. Neurobiol. Dis., 71. S. 169 - 180. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1095-953X

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Abstract

Histopathological studies on the brains of tauopathy cases including cases with Alzheimer's disease (AD) demonstrate that neurons with hyperphosphorylated protein tau display granulovacuolar degeneration (GVD), as evidenced by vacuolar lesions harboring a central granule, together with markers of the activated unfolded protein response (UPR). In order to examine whether this hallmark is reproduced in animal models we studied the presence of GVD and the activated UPR in two complementary mouse models, pR5 mice with a tau pathology and APPSLxPS1mut mice with an amyloid plaque pathology. Neither GVD nor a significant activation of the UPR was found in both APPSLxPS1mut mice and in those regions in the pR5 brain where only neurons with an early stage of tau hyperphosphorylation were present In contrast, those neurons that displayed a tau phospho-epitope signature that only appeared in old pR5 mice and also correlated with Gallyas-positive tangle staining harbored granulovacuolar lesions that were labeled with the GVD markers casein kinases 1 delta and 1 epsilon. Granulovacuolar lesions in pR5 mice were also labeled with the UPR markers phosphorylated PKR-like endoplasmic reticulum kinase, phosphorylated inositol-requiring enzyme 1 alpha and phosphorylated eukaryotic initiation factor 2 alpha. However, GVD was rarely observed in neurons bearing mature neurofibrillary tangles as evidenced by Congo red staining. Our results suggest that NFT-formation activates the UPR in pR5 mice and that it is the early stages of neurofibrillary tangle formation that are accompanied by GVD, in line with observations from studies on human autopsy cases. (C) 2014 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Koehler, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinekov, Maja UNSPECIFIED UNSPECIFIED UNSPECIFIED Goetz, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-425392
DOI:	10.1016/j.nbd.2014.07.006
Journal or Publication Title:	Neurobiol. Dis.
Volume:	71
Page Range:	S. 169 - 180
Date:	2014
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1095-953X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GLYCOGEN-SYNTHASE KINASE-3; ALZHEIMERS-DISEASE; TAU PATHOLOGY; NEUROFIBRILLARY TANGLES; PRECURSOR PROTEIN; ER STRESS; 1 DELTA; ACTIVATION; MICE; PHOSPHORYLATION Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42539