The modeling of Alzheimer's disease by the overexpression of mutant Presenilin 1 in human embryonic stem cells

• Honda, Makoto

  Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University

• Minami, Itsunari

  Department of Neurology, Kyoto University Graduate School of Medicine

• Tooi, Norie

  School of Human Health Sciences, Kyoto University Graduate School of Medicine

• Morone, Nobuhiro

  Institute for Frontier Medical Sciences, Kyoto University

• Nishioka, Hisae

• Uemura, Kengo

• Kinoshita, Ayae

• Heuser, John E.

• Nakatsuji, Norio

• Aiba, Kazuhiro

Abstract

Cellular disease models are useful tools for Alzheimer's disease (AD) research. Pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), are promising materials for creating cellular models of such diseases. In the present study, we established cellular models of AD in hESCs that overexpressed the mutant Presenilin 1 (PS1) gene with the use of a site-specific gene integration system. The overexpression of PS1 did not affect the undifferentiated status or the neural differentiation ability of the hESCs. We found increases in the ratios of amyloid-β 42 (Aβ42)/Aβ40 and Aβ43/Aβ40. Furthermore, synaptic dysfunction was observed in a cellular model of AD that overexpressed mutant PS1. These results suggest that the AD phenotypes, in particular, the electrophysiological abnormality of the synapses in our AD models might be useful for AD research and drug discovery.

Journal

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 469 587-592, 2016-01-15

  Academic Press Inc.

Keywords

• Alzheimer's disease
• Cellular disease model
• Human embryonic stem cell
• Presenilin 1
• Synaptic dysfunction

Details

• CRID: 1050282810817815168
• NII Article ID: 120005980892
• ISSN: 10902104
• ISSN: 0006291X
• HANDLE: 2433/218506
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles