Accumulation of b amyloid (Ab) peptides to nerve cells should be associated with the onset of Alzheimer's disease (AD). We prepared hybrid liposomes (HL) composed of 90 mol% phospholipids having various charged head groups (cationic L-a-dimyristoyltrimethyl ammonium propane (DMTAP), anionic L-a-dimyristoylphosphatidylserine (DMPS) or zwitterionic L-a-dimyristoylphosphatidylcholine (DMPC)) and 10 mol% polyoxyethylene(23) dodecyl ether (C 12 (EO) 23 )), and investigated the inhibitory eŠects of HL on the accumulation of Ab 1 40 peptides into human neuroblastoma (SH-SY5Y) cells in vitro. It is noteworthy that remarkable inhibitory eŠects on the accumulation of Ab 1 40 peptides were observed for SH-SY5Y cells treated with anionic HL-DMPS, though the accumulation was not inhibited by cationic HL-DMTAP. On the other hand, the immediate fusion of HL-DMTAP into SH-SY5Y cells was conrmed using a confocal laser microscope. Interestingly, the speciˆc interactions between anionic HL-DMPS and Ab 1 40 peptides were observed using the thio‰avin T (ThT) assay. In addition, the cytotoxicity of Ab 1 42 peptides on the SH-SY5Y cells decreased after the treatment with HL-DMPS. These results suggest that anionic HL-DMPS could be used as a novel medicine for AD in the future.