not a developmental effect. The decrease in GABAergic neuron numbers occurred during the late stage of neuronal differentiation of apoE4/4-hiPSCs, suggesting that apoE4 induces GABAergic neurodegeneration/loss. Importantly, apoE3/3-hiPSCs and apoE4/4-hiPSCs had similar efficiencies in generating Tbr1-positive glutamatergic neurons and TH-positive dopaminergic neurons in culture (Supplementary Fig. 4), suggesting a specific detrimental effect of apoE4 on GABAergic neurons. Furthermore, ~60% of GABAergic neurons derived from apoE4/4-hiPSCs, but only ~30% of those derived from apoE3/3-hiPSCs, were immunopositive for p-tau (Fig. 3f–h).
