title: Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness.
abstract: Oligomeric forms of amyloid-β peptide (Aβ) are thought to play a pivotal role in the pathogenesis of Alzheimer's disease (AD), but the mechanism involved is still unclear. Here, we generated induced pluripotent stem cells (iPSCs) from familial and sporadic AD patients and differentiated them into neural cells. Aβ oligomers accumulated in iPSC-derived neurons and astrocytes in cells from patients with a familial amyloid precursor protein (APP)-E693Δ mutation and sporadic AD, leading to endoplasmic reticulum (ER) and oxidative stress. The accumulated Aβ oligomers were not proteolytically resistant, and docosahexaenoic acid (DHA) treatment alleviated the stress responses in the AD neural cells. Differential manifestation of ER stress and DHA responsiveness may help explain variable clinical results obtained with the use of DHA treatment and suggests that DHA may in fact be effective for a subset of patients. It also illustrates how patient-specific iPSCs can be useful for analyzing AD pathogenesis and evaluating drugs.
authors: Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
authors: Takayuki
authors: T
authors: Kondo
authors: Masashi
authors: M
authors: Asai
authors: Kayoko
authors: K
authors: Tsukita
authors: Yumiko
authors: Y
authors: Kutoku
authors: Yutaka
authors: Y
authors: Ohsawa
authors: Yoshihide
authors: Y
authors: Sunada
authors: Keiko
authors: K
authors: Imamura
authors: Naohiro
authors: N
authors: Egawa
authors: Naoki
authors: N
authors: Yahata
authors: Keisuke
authors: K
authors: Okita
authors: Kazutoshi
authors: K
authors: Takahashi
authors: Isao
authors: I
authors: Asaka
authors: Takashi
authors: T
authors: Aoi
authors: Akira
authors: A
authors: Watanabe
authors: Kaori
authors: K
authors: Watanabe
authors: Chie
authors: C
authors: Kadoya
authors: Rie
authors: R
authors: Nakano
authors: Dai
authors: D
authors: Watanabe
authors: Kei
authors: K
authors: Maruyama
authors: Osamu
authors: O
authors: Hori
authors: Satoshi
authors: S
authors: Hibino
authors: Tominari
authors: T
authors: Choshi
authors: Tatsutoshi
authors: T
authors: Nakahata
authors: Hiroyuki
authors: H
authors: Hioki
authors: Takeshi
authors: T
authors: Kaneko
authors: Motoko
authors: M
authors: Naitoh
authors: Katsuhiro
authors: K
authors: Yoshikawa
authors: Satoko
authors: S
authors: Yamawaki
authors: Shigehiko
authors: S
authors: Suzuki
authors: Ryuji
authors: R
authors: Hata
authors: Shu-Ichi
authors: S
authors: Ueno
authors: Tsuneyoshi
authors: T
authors: Seki
authors: Kazuhiro
authors: K
authors: Kobayashi
authors: Tatsushi
authors: T
authors: Toda
authors: Kazuma
authors: K
authors: Murakami
authors: Kazuhiro
authors: K
authors: Irie
authors: William L
authors: WL
authors: Klein
authors: Hiroshi
authors: H
authors: Mori
authors: Takashi
authors: T
authors: Asada
authors: Ryosuke
authors: R
authors: Takahashi
authors: Nobuhisa
authors: N
authors: Iwata
authors: Shinya
authors: S
authors: Yamanaka
authors: Haruhisa
authors: H
authors: Inoue
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D050505:Mutant Proteins; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D020836:Protein Structure, Quaternary
chemical_list: D016229:Amyloid beta-Peptides; D050505:Mutant Proteins; D004281:Docosahexaenoic Acids