title: Cholesterol inhibits the insertion of the Alzheimer's peptide Abeta(25-35) in lipid bilayers.
abstract: The physiological relationship between brain cholesterol content and the action of amyloid beta (Abeta) peptide in Alzheimer's disease (AD) is a highly controversially discussed topic. Evidences for modulations of the Abeta/membrane interaction induced by plasma membrane cholesterol have already been observed. We have recently reported that Abeta(25-35) is capable of inserting in lipid membranes and perturbing their structure. Applying neutron diffraction and selective deuteration, we now demonstrate that cholesterol alters, at the molecular level, the capability of Abeta(25-35) to penetrate into the lipid bilayers; in particular, a molar weight content of 20% of cholesterol hinders the intercalation of monomeric Abeta(25-35) completely. At very low cholesterol content (about 1% molar weight) the location of the C-terminal part of Abeta(25-35) has been unequivocally established in the hydrocarbon region of the membrane, in agreement with our previous results on pure phospholipids membrane. These results link a structural property to a physiological and functional behavior and point to a therapeutical approach to prevent the AD by modulation of membrane properties.
authors: Physical Biochemistry, Darmstadt University of Technology, Petersenstrasse 22, 64287, Darmstadt, Germany. silvia.dante@hmi.de
authors: Silvia
authors: S
authors: Dante
authors: Thomas
authors: T
authors: Hauss
authors: Norbert A
authors: NA
authors: Dencher