Magnetic Levitational Assembly of Differentiated SH-SY5Y Cells for Aβ-Induced 3D Alzheimer's Disease Modeling and Curcumin Screening

Abstract

Alzheimer's disease is one of the prevalent neurodegenerative diseases and is characterized by amyloid beta aggregate (Aβ) accumulation. This study reports an Aβ 1–42 induced 3D Alzheimer's disease modeling utilizing differentiated SH-SY5Y spheroids, which is carried out by Magnetic levitation approach, and the neuroprotective effect of Curcumin is further investigated on this model. For this purpose, SH-SY5Y spheroids are differentiated using Retinoic acid-Brain-derived neurotrophic factor sequentially during 3D cell culture. Differentiated spheroids maintained high viability and exhibited significant neuronal characteristics, as evidenced by increasing β-III tubulin and NeuN expressions. 3D Alzheimer's disease model formation and neurotoxicity of Aβ 1–42 aggregates are investigated on un-/differentiated spheroids, resulting in 65% and 51% cell viability, respectively. Characterization of the 3D Alzheimer's disease model is done by immunostaining of Choline acetyltransferase to investigate cholinergic neuron activity loss, showing a 2.2 decrease in fluorescence intensity. Further, Curcumin treatment on the 3D Alzheimer's disease model resulted in augmenting cell viability, confirming neuroprotective effect of Curcumin on Aβ 1–42 induced Alzheimer's disease model. This study highlighted the magnetic levitation-based fabrication of Aβ 1-42-induced 3D Alzheimer's disease model successfully, offering a promising experimental platform for other neurodegenerative disease research and potential clinical applications.