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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Bergström P,Agholme L,Nazir FH,Satir TM,Toombs J,Wellington H,Strandberg J,Bontell TO,Kvartsberg H,Holmström M,Boreström C,Simonsson S,Kunath T,Lindahl A,Blennow K,Hanse E,Portelius E,Wray S,Zetterberg Hdoi
10.1038/srep29200subject
Has Abstractpub_date
2016-07-07 00:00:00pages
29200issn
2045-2322pii
srep29200journal_volume
6pub_type
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