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ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 16 - 2024 |
doi: 10.3389/fnagi.2024.1435445
Modeling APOE ε4 Familial Alzheimer's Disease in Directly Converted 3D Brain Organoids
Provisionally accepted- 1 Dongguk University Seoul, Seoul, Republic of Korea
- 2 Rutgers, The State University of New Jersey, New Jersey, United States
Brain organoids have become a valuable tool for studying human brain development, disease modeling, and drug testing. However, generating brain organoids with mature neurons is time-intensive and often incomplete, limiting their utility in studying age-related neurodegenerative diseases such as Alzheimer’s disease (AD). Here, we report the generation of 3D brain organoids from human fibroblasts through direct reprogramming, with simplicity, efficiency, and reduced variability. We also demonstrate that induced brain organoids from APOE ε4 AD patient fibroblasts capture some disease-specific features and pathologies associated with APOE ε4 AD. Moreover, APOE ε4-induced brain organoids with mutant APP overexpression faithfully recapitulate the acceleration of AD-related pathologies, providing a more physiologically relevant and patient-specific model of familial AD. Importantly, transcriptome analysis reveals that gene sets specific to APOE ε4 patient-induced brain organoids are highly similar to those of APOE ε4 post-mortem AD brains. Overall, induced brain organoids from direct reprogramming offer a promising approach for more efficient and controlled studies of neurodegenerative disease modeling.
Keywords: Alzheimer's disease, direct conversion, 3D modeling, Apolipoprotein E, Amyloid beta
Received: 20 May 2024; Accepted: 25 Jul 2024.
Copyright: © 2024 KIM, Kim, Hongwon, Cho, An, Kang and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
JONGPIL KIM, Dongguk University Seoul, Seoul, Republic of Korea
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