Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons.
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.
Schneider
Anja
A
Center for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
Schulz-Schaeffer
Walter
W
Hartmann
Tobias
T
Schulz
Jörg B
JB
Simons
Mikael
M
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
D016229:Amyloid beta-Peptides; D008563:Membrane Lipids; D002784:Cholesterol