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Open Access 01-12-2014 | Research

Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression

Authors: Sascha W Weyer, Marta Zagrebelsky, Ulrike Herrmann, Meike Hick, Lennard Ganss, Julia Gobbert, Morna Gruber, Christine Altmann, Martin Korte, Thomas Deller, Ulrike C Müller

Published in: Acta Neuropathologica Communications | Issue 1/2014

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.

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Title: Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression
Authors: Sascha W Weyer
Marta Zagrebelsky
Ulrike Herrmann
Meike Hick
Lennard Ganss
Julia Gobbert
Morna Gruber
Christine Altmann
Martin Korte
Thomas Deller
Ulrike C Müller
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2014
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-2-36

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Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression

Abstract

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Abstract

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