title: Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression
creator: Weyer, Sascha W.
creator: Zagrebelsky, Marta
creator: Herrmann, Ulrike
creator: Hick, Meike
creator: Ganß, Lennard
creator: Gobbert, Julia
creator: Gruber, Morna
creator: Altmann, Christine
creator: Korte, Martin
creator: Deller, Thomas
creator: Müller, Ulrike C.
subject: ddc-570
subject: 570 Life sciences
subject: ddc-610
subject: 610 Medical sciences Medicine
description: 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.
publisher: Biomed Central
date: 2014
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/18671/1/40478_2014_Article_108.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-186712
identifier:   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     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/18671/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng