title: Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons.
abstract: A key event in the pathogenesis of Alzheimer's disease is the conversion of soluble amyloid Abeta-peptide into toxic aggregates. Here, we studied the effect of cholesterol depletion on the formation of insoluble Abeta. We found that reduction of neuronal cholesterol by approximately 25% reduced the neuronal formation of insoluble Abeta without affecting the secretion of soluble Abeta. Moreover, we demonstrate that Abeta-oligomers from Alzheimer's disease brains associate with a detergent-resistant membrane fraction in a cholesterol-dependent manner. These results suggest a key role for cholesterol in aggregation of Abeta.
authors.affiliation: Center for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schneider
authors.forename: Walter
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000172:deficiency*; D015536:Down-Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D008563:Membrane Lipids; D002784:Cholesterol