Western blot analysis with p-tau-specific antibodies (AT8, AT180, PHF1, and AT270) revealed significantly higher p-tau levels in apoE4/4 neurons than apoE3/3 neurons, both in individual lines (Supplementary Fig. 2c–f) and as shown by mean values (Fig. 1f–j). Double immunostaining with anti-p-tau (AT8 or PHF1) and anti-MAP2 antibodies consistently showed that significantly higher percentages of apoE4/4 neurons were also positive for p-tau (Fig. 1k–m). Furthermore, p-tau accumulated mostly in the soma and dendrites of apoE4/4 neurons, suggesting that apoE4 induces both tau phosphorylation and mislocalization of p-tau in human neurons, a pathological hallmark of p-tau in AD brains1,20,21.
