Exp Neurobiol.
2019 Jun;28(3):329-336. 10.5607/en.2019.28.3.329.
The First Generation of iPSC Line from a Korean Alzheimer's Disease Patient Carrying APP-V715M Mutation Exhibits a Distinct Mitochondrial Dysfunction
- Affiliations
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- 1CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seongnam 13488, Korea. jsong5873@gmail.com
- 2Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
- 3Neuroscience Center, Samsung Medical Center, Seoul 06351, Korea. dukna@naver.com
- 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
- 5Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8561, Japan.
- 6Dong-A Socio R&D Center, Dong-A ST, Yongin 17073, Korea.
- 7Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Korea.
- 8Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.
- KMID: 2451069
- DOI: http://doi.org/10.5607/en.2019.28.3.329
Abstract
- Alzheimer's Disease (AD) is a progressive neurodegenerative disease, which is pathologically defined by the accumulation of amyloid plaques and hyper-phosphorylated tau aggregates in the brain. Mitochondrial dysfunction is also a prominent feature in AD, and the extracellular Aβ and phosphorylated tau result in the impaired mitochondrial dynamics. In this study, we generated an induced pluripotent stem cell (iPSC) line from an AD patient with amyloid precursor protein (APP) mutation (Val715Met; APP-V715M) for the first time. We demonstrated that both extracellular and intracellular levels of Aβ were dramatically increased in the APP-V715M iPSC-derived neurons. Furthermore, the APP-V715M iPSC-derived neurons exhibited high expression levels of phosphorylated tau (AT8), which was also detected in the soma and neurites by immunocytochemistry. We next investigated mitochondrial dynamics in the iPSC-derived neurons using Mito-tracker, which showed a significant decrease of anterograde and retrograde velocity in the APP-V715M iPSC-derived neurons. We also found that as the Aβ and tau pathology accumulates, fusion-related protein Mfn1 was decreased, whereas fission-related protein DRP1 was increased in the APP-V715M iPSC-derived neurons, compared with the control group. Taken together, we established the first iPSC line derived from an AD patient carrying APP-V715M mutation and showed that this iPSC-derived neurons exhibited typical AD pathological features, including a distinct mitochondrial dysfunction.
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