eprintid: 18671
rev_number: 17
eprint_status: archive
userid: 1589
dir: disk0/00/01/86/71
datestamp: 2015-05-27 08:50:15
lastmod: 2024-05-06 13:17:55
status_changed: 2015-05-27 08:50:15
type: article
metadata_visibility: show
creators_name: Weyer, Sascha W.
creators_name: Zagrebelsky, Marta
creators_name: Herrmann, Ulrike
creators_name: Hick, Meike
creators_name: Ganß, Lennard
creators_name: Gobbert, Julia
creators_name: Gruber, Morna
creators_name: Altmann, Christine
creators_name: Korte, Martin
creators_name: Deller, Thomas
creators_name: Müller, Ulrike C.
title: Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression
subjects: ddc-570
subjects: ddc-610
divisions: i-160100
divisions: i-912000
abstract: Synaptic dysfunction and synapse loss are key features of Alzheimer’s pathogenesis. Previously, we showed an essential function of APP and APLP2 for synaptic plasticity, learning and memory. Here, we used organotypic hippocampal cultures to investigate the specific role(s) of APP family members and their fragments for dendritic complexity and spine formation of principal neurons within the hippocampus. Whereas CA1 neurons from APLP1-KO or APLP2-KO mice showed normal neuronal morphology and spine density, APP-KO mice revealed a highly reduced dendritic complexity in mid-apical dendrites. Despite unaltered morphology of APLP2-KO neurons, combined APP/APLP2-DKO mutants showed an additional branching defect in proximal apical dendrites, indicating redundancy and a combined function of APP and APLP2 for dendritic architecture. Remarkably, APP-KO neurons showed a pronounced decrease in spine density and reductions in the number of mushroom spines. No further decrease in spine density, however, was detectable in APP/APLP2-DKO mice. Mechanistically, using APPsα-KI mice lacking transmembrane APP and expressing solely the secreted APPsα fragment we demonstrate that APPsα expression alone is sufficient to prevent the defects in spine density observed in APP-KO mice. Collectively, these studies reveal a combined role of APP and APLP2 for dendritic architecture and a unique function of secreted APPs for spine density.
date: 2014
publisher: Biomed Central
id_scheme: DOI
ppn_swb: 1657058522
own_urn: urn:nbn:de:bsz:16-heidok-186712
language: eng
bibsort: WEYERSASCHCOMPARATIV2014
full_text_status: public
publication: Acta Neuropathologica Communications
volume: 2
number: 36
place_of_pub: London
pagerange: 1-15
issn: 2051-5960
citation:   Weyer, Sascha W. ; Zagrebelsky, Marta ; Herrmann, Ulrike ; Hick, Meike ; Ganß, Lennard ; Gobbert, Julia ; Gruber, Morna ; Altmann, Christine ; Korte, Martin ; Deller, Thomas ; Müller, Ulrike C.  (2014) Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression.  Acta Neuropathologica Communications, 2 (36).  pp. 1-15.  ISSN 2051-5960     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/18671/1/40478_2014_Article_108.pdf