Journal
NEUROSCIENCE LETTERS
Volume 639, Issue -, Pages 74-81Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2016.12.060
Keywords
Alzheimer's disease; Induced pluripotent stem cells; Amyloid-beta; Neurotoxicity
Categories
Funding
- UT Brain Initiative
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Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients. iPSC lines were differentiated into neuronal precursors (iPSC-NPCs) and neurons that were subjected to amyloid beta (A beta) toxicity assays. We found that neurons derived from the fAD patient have a higher susceptibility to A beta 1-42 oligomers compared with neurons coming from healthy and sAD individuals. Our findings suggest that neurons from patients with PSEN1-A246E mutation have intrinsic properties that make them more susceptible to the toxic effects of A beta 1-42 oligomers in the AD brain. (C) 2017 Elsevier Ireland Ltd. All rights reserved.
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