Autophagy and neuroinflammation modulation by nano-graphene oxide in PSEN1 Alzheimer’s brain organoids

Background Alzheimer’s disease (AD) is one of the best-known neurodegenerative diseases, and substantial progress has been made in the field of neuroscience and AD. However, there has been no major improvement in AD treatment. Methods Cerebral organoids were generated using induced pluripotent stem cells (iPSCs) from both healthy individual and AD patients. Organoids were cultured for 12 weeks and then nano-graphene oxide (NGO) was treated for another 2 weeks. Organoids were then sampled according to different sampling methods for various analysis. Results AD patient-derived iPSCs were employed to generate cerebral brain organoids and were cultured until they expressed AD phenotypes, accumulation of amyloid-beta (Aβ) plaquesand hyperphosphorylated tau (pTau)-derived neurofibrillary tangles (NFTs). We investigated whether NGO treatment could decrease the expression of the major hallmarks of AD. Our study illustrates that accumulated Aβ plaques were diminished in the NGO-treated AD organoids. NGO activates the autophagy pathway, targeting AMPK activation. The changes in the levels of AMP and ADP in NGO treated group suggest that NGO affects cellular energy metabolism, thus activating AMPK autophagic pathway. Also, the astrocytes and microglial cell presence in our model allowed examining further into inflammatory effect of NGO. The decrease in proinflammatory cytokine levels in NGO treated group led to decrease in IFITM3 expression and going further into diminishing γ-secretase activity. Conclusions Overall, the development of AD brain organoids successfully mimickedAD phenotype expression;thus, they could be used as a screening platform for novel AD treatment assessments.