title: The modeling of Alzheimer's disease by the overexpression of mutant Presenilin 1 in human embryonic stem cells.
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.
authors.affiliation: Stem Cell and Drug Discovery Institute, Kyoto 600-8813, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Honda
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Itsunari
authors.initials: I
authors.lastname: Minami
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Norie
authors.initials: N
authors.lastname: Tooi
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Morone
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hisae
authors.initials: H
authors.lastname: Nishioka
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
authors.affiliation: School of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan; Department of Cell Biology, Washington University, St. Louis, MO 63110, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Heuser
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan; Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.affiliation: Stem Cell and Drug Discovery Institute, Kyoto 600-8813, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan. Electronic address: kaiba@icems.kyoto-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Aiba
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D000066449:Human Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009154:Mutation; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D053764:Presenilin-1
keywords: Alzheimer's disease; Cellular disease model; Human embryonic stem cell; Presenilin 1; Synaptic dysfunction