Fig. 5e,f). Importantly, p-tau accumulated in degenerating (beading) axons, as determined by anti-p-tau (PHF1) and anti-total tau double immunostaining, in apoE4/4-GABAergic neurons, but not in apoE3/3-GABAergic neurons at 5 weeks of culture (Fig. 3l,m). As in AD brains, p-tau also mislocalized to dendrites of apoE4/4-GABAergic neurons, but not much in apoE3/3-GABAergic neurons, as revealed by anti-p-tau (PHF1) and anti-MAP2 double immunostaining (Supplementary Fig. 5h,i). Quantification of Caspase-3 and GABA double positive cells suggested significantly more apoptotic cell death of apoE4/4-GABAergic neurons than apoE3/3-GABAergic neurons (Supplementary Fig. 5g). Taken together, these data demonstrate clearly that apoE4 induces human GABAergic neuron degeneration/death in culture.
