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Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation

Bergstrom, P; Agholme, L; Nazir, FH; Satir, TM; Toombs, J; Wellington, H; Strandberg, J; ... Zetterberg, H; + view all (2016) Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation. Scientific Reports , 6 , Article 292. 10.1038/srep29200. Green open access

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Abstract

Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer’s disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. α-Cleaved soluble APP (sAPPα) was secreted early during differentiation, from neuronal progenitors, while β-cleaved soluble APP (sAPPβ) was first secreted after deep-layer neurons had formed. Short Aβ peptides, including Aβ1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Aβ1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Aβ1-40/42, is associated with mature neuronal phenotypes.

Type: Article
Title: Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/srep29200
Publisher version: http://dx.doi.org/10.1038/srep29200
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, PLURIPOTENT STEM-CELLS, CEREBRAL-CORTEX DEVELOPMENT, ALZHEIMERS-DISEASE, CEREBROSPINAL-FLUID, SECRETASE CLEAVAGE, IN-VIVO, PEPTIDES, MUTATION, DOMAIN, BACE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1516258
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