Authors
Won Hee Jung, Seung Tack Oh, Mu Seog Choe, Yu Jin Kwon, So Jin Kim, Ye Seong Jeon, Kyung Min Baek, Woochul Chang, Kyung Seob Lim, Joong Sun Kim, Seung Pil Yun, Min Young Lee
Published in
International journal of stem cells. Jul 29, 2026. Epub Jul 29, 2026.
Abstract
Various animal and cellular Alzheimer's disease (AD) models harboring familial AD (fAD) mutations have been developed and widely used for AD research. In this study, we established an AD cerebral organoid (CO) model using a novel Val669Leu (APPSeoul) mutation in the APP gene. We generated a human embryonic stem cell (hESC) line overexpressing APPSeoul, referred to as the fAD-S hESC line. Using this line, we produced COs and confirmed robust AD-associated pathologies, including amyloid-β (Aβ) accumulation and tau phosphorylation. In addition, increased expression of β-secretase was observed in this model. Based on these findings, we investigated the effects of BACE1 inhibitor IV, a β-secretase inhibitor, in the CO model. Treatment with BACE1 inhibitor IV significantly reduced Aβ levels and tau phosphorylation. Furthermore, we differentiated the fAD-S hESC line into cortical neurons (fAD-S neurons) to establish a 2D cellular AD model. Consistent with the CO results, fAD-S neurons exhibited elevated levels of Aβ and phosphorylated tau, which were also significantly attenuated by BACE1 inhibitor IV treatment. Collectively, these results demonstrate the successful establishment of hESC-derived 2D and 3D AD models based on the APPSeoul fAD mutation.
PMID:
42521490
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.
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