Fig. 6. CRISPR/SpCas9-HF1-mediated reduction of BACE2 copy number from three to two in the T21C5 hiPSC line provoked early AD-like pathology in organoids.
a–c Early AD-like pathology was provoked in 41DIV T21C5Δ7 organoids, but was not detected in T21C5 parental organoids. a–b Treatment of the T21C5Δ7 with combined βI-IV (β-sectretase inhibitor) and compound E (γ-secretase inhibitor) from 20 to 41DIV completely prevented the formation of extracellular amyloid deposits. Staining with amyloid specific dye (AmyloGlo) and nuclear dye (DRAQ5). Scale bar 50 μm. c β- and γ-secretase inhibitor treatment highly significantly reduced the presence of TG3+ (pathologically conformed Tau) cells in T21C5Δ7 organoids compared with untreated T21C5Δ7 organoids. Scale bar: 20 μm. Error bars: SD, ****p < 0.0001. Only statistically significant differences are shown.