in close agreement with that observed in the scaffolded 3D cultures of Choi et al. 2014; [40]. Additionally, the inhibition of Aβ production using β and γ-secretase inhibitors reduced tau hyperphosphorylation only at the later time point of treatment, after Aβ reduction was observed. Thus, AD-relevant phenotypes of Aβ accumulation emerge prior to tauopathy in this model. Moreover, the reductions in Aβ accumulation that occur from the inhibition of APP processing lead to a dose- and time-dependent amelioration of tauopathy in the fAD organoids, suggesting a causal relationship between these relevant pathologies in the neural organoid model.
