TY  - JOUR
A1  - Weyer, Sascha W.
A1  - Zagrebelsky, Marta
A1  - Herrmann, Ulrike
A1  - Hick, Meike
A1  - Ganss, Lennard
A1  - Gobbert, Julia
A1  - Gruber, Morna
A1  - Altmann, Christine
A1  - Korte, Martin
A1  - Deller, Thomas
A1  - Müller, Ulrike C.
T1  - Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPα expression
T2  - Acta Neuropathologica Communications
N2  - 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 APPsalpha-KI mice lacking transmembrane APP and expressing solely the secreted APPsalpha fragment we demonstrate that APPsalpha 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.
KW  - Alzheimer
KW  - Amyloid precursor protein
KW  - Neuronal morphology
KW  - Spine density
KW  - Knockout
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/33402
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-334027
SN  - 2051-5960
N1  - © 2014 Weyer et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 2
IS  - Art. 36
SP  - 1
EP  - 15
PB  - BioMed Central
CY  - London
ER  -