How does ApoE stimulate Aβ synthesis? In rodent neurons, ApoE activates multiple signaling pathways, including MAP-kinases (Ohkubo et al., 2001; Qiu et al., 2004). Confirming these studies, we found that ApoE increased ERK1/2 phosphorylation in human neurons 2- to 5-fold (Fig. 2A). Strikingly, ApoE2, ApoE3, and ApoE4 again exhibited the same differential efficacy in this stimulation as for Aβ synthesis (ApoE4>ApoE3>ApoE2).
