Similar to Aβ synthesis, ApoE3 had no effect on APP levels in human neurons co-cultured with glia (Fig. S1H, S5A–S5C), presumably because glial factors fully activate the non-canonical MAP-kinase pathway that stimulates APP transcription. Consistent with this hypothesis, DLK knockdowns or DLK inhibition by MBIP dramatically decreased APP and Aβ40 and Aβ42 levels in neurons co-cultured with glia, whereas DLK overexpression significantly increased these levels (Fig. S5A–S5C).
