Cholesterol modulates the membrane-disordering effects of beta-amyloid peptides in the hippocampus: specific changes in Alzheimer's disease.
Cholesterol represents an important determinant of the physical state of biological membranes. In Alzheimer's disease (AD) brains, specific changes in the distribution of cholesterol and its membrane-ordering effects take place. In the present study, membrane fluidity was investigated at the level of the hydrocarbon core and of the heads of the phospholipid bilayers using two different fluorescent probes. Hippocampal membranes of AD brains showed a reduced fluidity in the hydrocarbon core region only. Fluidity was correlated with the cholesterol content in AD and control membranes. Aggregated beta-amyloid peptides (Abeta) disrupted brain membrane structure in AD patients and controls in the same fashion. However, this effect was correlated with the cholesterol content in AD membranes only. It is suggested that in AD the brain becomes specifically sensitive for the modulation by membrane-bound cholesterol of the membrane-disturbing and ultimately neurotoxic properties of Abeta.
Eckert
G P
GP
Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany.
Cairns
N J
NJ
Maras
A
A
Gattaz
W F
WF
Müller
W E
WE
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D016880:Anisotropy; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism*; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D005454:Fluorescence Polarization / Q000379:methods; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D004161:Diphenylhexatriene; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D002784:Cholesterol