Lysophosphatidylcholine modulates fibril formation of amyloid beta peptide

Phospholipids are known to influence fibril formation of amyloid beta (Ab) peptide. Here, we show that lysophosphatidylcholine (LPC), a polar phospholipid, enhances A beta(1-42) fibril formation, by decreasing the lag time and the critical peptide concentration required for fibril formation, and increasing the fibril elongation rate. Conversely, LPC did not have an enhancing effect on A beta(1-40) fibril formation, and appeared to be inhibitory. Tyrosine fluorescence spectroscopy showed that LPC altered the fluorescence spectra of A beta(1-40) and A beta(1-42) in opposite ways. Further, 8-anilino-1-naphthalene sulfonic acid fluorescence spectroscopy showed that LPC significantly increased the hydrophobicity of A beta(1-42), but not of A beta(1-40). Tris-tricine gradient SDS/PAGE revealed that LPC increased the formation of higher-molecular-weight species of A beta(1-42), including trimers and tetramers. LPC had no such effect on A beta(1-40), and thus may specifically influence the oligomerization and nucleation processes of A beta(1-42) in a manner dependent on its native structure. Dot-blot assays confirmed that LPC induced A beta(1-42) oligomer formation at an early time point. Thus our results indicate that LPC specifically enhances the formation of A beta(1-42) fibrils, the main component of senile plaques in Alzheimer's disease patients, and may be involved in Alzheimer's disease pathology.