ApoE-derived peptides significantly decrease Aβ1-40 levels in primary cortical neuronal cells. Primary cortical neurons were treated with apoE monomer (n = 6, A), dimer (n = 6, B), or trimer (n = 6, C) for 24 h, and Aβ1-40 levels in the conditioned media were determined by ELISA (n = 6). Treatment of primary neurons with apoE dimer decreased Aβ1-40 by 19% at 500 nM (p < 0.05) and 27% at 1 μM (p < 0.01). Treatment with apoE trimer decreased Aβ1-40 by 12% at 100 nM (p < 0.05), 18% at 500 nM (p < 0.05), and 28% at 1 μM (p < 0.001). D. Rodent Aβ1-40 was measured from samples containing the apoE dimer peptide alone, synthetic rodent Aβ40 alone, synthetic rodent Aβ40 with PBS, or synthetic rodent Aβ40 with apoE dimer peptide. Aβ1-40 values were normalized to background with apoE dimer peptide alone, and were not found to be significantly different in the presence of PBS or apoE dimer peptide.