Journal of Alzheimer's Disease
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Home > Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness.

TitleModeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness.
Publication TypeJournal Article
Year of Publication2013
AuthorsKondo, T, Asai, M, Tsukita, K, Kutoku, Y, Ohsawa, Y, Sunada, Y, Imamura, K, Egawa, N, Yahata, N, Okita, K, Takahashi, K, Asaka, I, Aoi, T, Watanabe, A, Watanabe, K, Kadoya, C, Nakano, R, Watanabe, D, Maruyama, K, Hori, O, Hibino, S, Choshi, T, Nakahata, T, Hioki, H, Kaneko, T, Naitoh, M, Yoshikawa, K, Yamawaki, S, Suzuki, S, Hata, R, Ueno, S-I, Seki, T, Kobayashi, K, Toda, T, Murakami, K, Irie, K, Klein, WL, Mori, H, Asada, T, Takahashi, R, Iwata, N, Yamanaka, S, Inoue, H
JournalCell Stem Cell
Volume12
Issue4
Pagination487-96
Date Published2013 Apr 4
ISSN1875-9777
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Cell Differentiation, Cerebral Cortex, Docosahexaenoic Acids, Humans, Induced Pluripotent Stem Cells, Intracellular Space, Models, Biological, Mutant Proteins, Neurons, Oxidative Stress, Phenotype, Protein Structure, Quaternary
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.

DOI10.1016/j.stem.2013.01.009
Alternate JournalCell Stem Cell
PubMed ID23434393
Top50 Topics: 
Amyloid beta, iPSC, Pathology, Pharmacology
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Source URL: https://www.j-alz.com/content/modeling-alzheimers-disease-ipscs-reveals-stress-phenotypes-associated-intracellular-a%CE%B2-and