Cholesterol binding to amyloid-beta fibrils: a TEM study.
There is increasing interest in the role of brain cholesterol in Alzheimer's disease and the contribution of cholesterol to the formation of amyloid plaques. This paper presents a TEM study showing the binding of soluble approximately 10 nm diameter cholesterol-PEG 600 micelles to amyloid-beta(1-42) (Abeta(1-42)) fibrils formed either in the presence of this cholesterol derivative or to preformed fibrils generated under four different fibrillogenesis conditions. Specimens negatively stained with uranyl acetate revealed that during 24 h fibrillogenesis at 37 degrees C the cholesterol-PEG micelles bound periodically to Abeta(1-42) protofibrils and apparently also formed a thin smooth unbroken coating on mature double helical fibrils. Preformed protofibrils, generated in water alone or in the presence of 0.1 mM cupric sulphate, also exhibited periodic binding of cholesterol-PEG micelles, indicating the inherently helical nature of the protofibril. Double helical mature Abeta(1-42) fibrils, generated in the presence of cholesterol microcrystals or hydrogen peroxide (1 mM), bound cholesterol-PEG micelles with no immediately apparent regularity and without creating a smooth coating. The differing capacities of the Abeta(1-42) protofibrils and mature double helical fibrils to bind cholesterol-PEG 600 may indicate differences in the accessibility of the micellar cholesterol to the purported Abeta(17-21) hydrophobic cholesterol-binding motif on the fibril surfaces.
Harris
J Robin
JR
Institute of Zoology, University of Mainz, D-55099 Mainz, Germany. rharris@uni-mainz.de
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D002784:Cholesterol / Q000737:chemistry*; D006801:Humans; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011092:Polyethylene Glycols / Q000737:chemistry
D000682:Amyloid; D016229:Amyloid beta-Peptides; D008823:Micelles; D011092:Polyethylene Glycols; D002784:Cholesterol