ApoE receptor inhibition alters tau phosphorylation. Primary neurons were pre-incubated in the presence of inhibitors ("i") (lanes 3 and 4) for 2h and then either exposed to control buffer ("C") (lanes 1 and 3) or 2 μM apoE peptide ("EP") (lane 2 and 4). Inhibitors used were RAP (1 μM), PP2 (1 μM), or PD98059 (10 μM). Cell extracts were was examined by immunoblots with AT8 (n = 4, left panel), AT270 (n = 4, middle panel) or 5E2(n = 4, right panel). RAP significantly reversed the effect of the apoE peptide on tau phosphorylation and total tau. PP2 and PD98059 treatments showed no significant changes. Panel B: Quantification of RAP blots (n = 4) demonstrated significant reversal of the effects that apoE (2uM) has on various tau and phospho-tau epitopes (p < 0.02).