In this study, we combined 3D neuronal cultures and iPSC technology to generate 3D neuro-spheroids from AD patients. To evaluate the utility of this paradigm, we focused on characterizing Aβ generation and drug inhibition in 3D cultures. Using quantitative Mass Spectrometry, we evaluated how drug penetration in 3D cultures differs from that in 2D cultures in which drug diffusion is not limited by compact cellular architecture. Thus, this system may be useful for evaluation of established neuronal features of the AD phenotype and for characterization of the effects of pharmacological agents on these features. These results are significant for future studies employing 3D iPSC-derived cultures to investigate AD pathology and treatment strategies.
