The Effect of Cholesterol and Monosialoganglioside (GM1) on the Release and Aggregation of Amyloid β-Peptide from Liposomes Prepared from Brain Membrane-like Lipids

• Published in: The Journal of biological chemistry 2004-04, Vol.279 (17), p.17587
• Main Authors: Yoshihiko Tashima, Ryoko Oe, Sannamu Lee, Gohsuke Sugihara, Eric J. Chambers, Mitsuo Takahashi, Tatsuo Yamada
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M308622200

In order to investigate the influence of cholesterol (Ch) and monosialoganglioside (GM1) on the release and subsequent deposition/aggregation of amyloid β peptide (Aβ)-(1–40) and Aβ-(1–42), we have examined Aβ peptide model membrane interactions by circular dichroism, turbidity measurements, and transmission electron microscopy (TEM). Model liposomes containing Aβ peptide and a lipid mixture composition similar to that found in the cerebral cortex membranes (CCM-lipid) have been prepared. In all, four Aβ-containing liposomes were investigated: CCM-lipid; liposomes with no GM1 (GM1-free lipid); those with no cholesterol (Ch-free lipid); liposomes with neither cholesterol nor GM1 (Ch-GM1-free lipid). In CCM liposomes, Aβ was rapidly released from membranes to form a well defined fibril structure. However, for the GM1-free lipid, Aβ was first released to yield a fibril structure about the membrane surface, then the membrane became disrupted resulting in the formation of small vesicles. In Ch-free lipid, a fibril structure with a phospholipid membrane-like shadow formed, but this differed from the well defined fibril structure seen for CCM-lipid. In Ch-GM1-free lipid, no fibril structure formed, possibly because of membrane solubilization by Aβ. The absence of fibril structure was noted at physiological extracellular pH (7.4) and also at liposomal/endosomal pH (5.5). Our results suggest a possible role for both Ch and GM1 in the membrane release of Aβ from brain lipid bilayers.