Universität zu Köln

Midani-Kurcak, Jiwana Sherin, Dinekov, Maja, Puladi, Behrus, Arzberger, Thomas and Koehler, Christoph (2019). Effect of tau-pathology on charged multivesicular body protein 2b (CHMP2B). Brain Res., 1706. S. 224 - 237. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1872-6240

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Abstract

Charged multivesicular body protein 2b (CHMP2B) is a subunit of the endosomal sorting complex required for transport (ESCRT)-III that mediates scission of budded membranes. Neurons with CHMP2B-positive granulovacuolar inclusions in the cytoplasm are much more frequent in hippocampi of cases with Alzheimer's disease when compared with controls. We analyzed immunolabeled brain sections from tau-transgenic mice, APP-transgenic mice, non-transgenic mice, and human hippocampi to investigate the relation between CHMP2B and tau and plaque pathology that are major histopathological features of Alzheimer's disease. Neurons undergoing granulovacuolar degeneration (GVD) were found in human hippocampi and old tau-trangenic mice but not in the APP-transgenic strains. 57% of neurons with GVD displayed GVD-granules double-labeled for CHMP2B and the GVD-marker casein kinase 1 delta in 24 months-old tau-transgenic mice and 5.7% of neurons with tau hyperphosphorylated at Thr212 and Ser214 (immunoreactive with antibody AT100) displayed CHMP2B-positive GVD-granules, in human hippocampi it was 100% and 46% respectively. The number of neurons with GVD-inclusions increased in tau-transgenic mice with the number of AT100-positive neurons, suggesting a link between tau-pathology and GVD. GVD-granules in human hippocampi also displayed immunoreactivity for Vps4a, another protein component of ESCRT-III. In cases with aging-related tau astrogliopathy (ARTAG), astrocytes containing hyper-phosphorylated tau immunoreactive with antibody AT8 displayed strong CHMP2B immunoreactivity. The results suggest dysregulation of CHMP2B together with tau-pathology and possibly a disturbance of the regulation of vesicular compartments. The absence of combined A beta- and tau-associated pathology in the transgenic mice may account for the difference in CHMP2B-immunoreactivity between the transgenic mice and human hippocampus.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Midani-Kurcak, Jiwana Sherin UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinekov, Maja UNSPECIFIED UNSPECIFIED UNSPECIFIED Puladi, Behrus UNSPECIFIED UNSPECIFIED UNSPECIFIED Arzberger, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehler, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-155808
DOI:	10.1016/j.brainres.2018.11.008
Journal or Publication Title:	Brain Res.
Volume:	1706
Page Range:	S. 224 - 237
Date:	2019
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1872-6240
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALZHEIMERS-DISEASE; GRANULOVACUOLAR DEGENERATION; FRONTOTEMPORAL DEMENTIA; ESCRT-III; TRANSGENIC MICE; SUBUNIT CHMP2B; MOUSE MODEL; PHOSPHORYLATION; BODIES; NEURONS Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15580