PhD Student Seoul National University Seoul, Republic of Korea
Abstract: Alzheimer’s disease (AD) remains one of the most prominent neurodegenerative disorders, with significant advances in understanding its pathophysiology and underlying mechanisms; however, therapeutic progress has been limited. In this study, patient-derived induced pluripotent stem cells (iPSCs) were utilized to generate cerebral brain organoids, which were cultured until they exhibited key AD phenotypes, including the accumulation of amyloid-beta (Aβ) plaques and the formation of hyperphosphorylated tau (pTau)-derived neurofibrillary tangles (NFTs). We aimed to evaluate whether treatment with nano graphene oxide (NGO) could mitigate the expression of these critical AD hallmarks. Although NGO treatment did not alter the levels of pTau, it significantly reduced the accumulation of Aβ plaques in AD organoids. Mechanistically, NGO treatment activated the autophagy pathway via AMP-activated protein kinase (AMPK) signaling and decreased the expression of IFITM3, which correlated with reduced pro-inflammatory cytokine levels. Collectively, the AD brain organoid model effectively recapitulated key disease phenotypes and provides a promising platform for evaluating potential therapeutic interventions in AD.
Funding Source: This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2023-00266110)
