Effects of beta-amyloid peptides on the fluidity of membranes from frontal and parietal lobes of human brain. High potencies of A beta 1-42 and A beta 1-43.
beta-amyloid peptide (A beta) and several A beta-fragments decrease the fluidity of human cortex membranes in a concentration dependent fashion. The effect of A beta on membrane fluidity increases with peptide length, is most pronounced for A beta 1-43 and can be seen at concentrations as low as 100 nmol/l. While the fragment A beta 25-35 is active, scrambled peptide (A beta 35-25) when investigated under similar conditions shows no effects on membrane fluidity. The effect of A beta peptides on fluidity of the phospholipid bilayer is more pronounced in the hydrocarbon core (labeled with the fluorescence probe 1,6-diphenylhexa-1,3,5-triene) than in the region of the hydrophilic heads (labeled with the fluorescence probe 1-[4'-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene). It is suggested that the effect of A beta on neuronal membranes is probably a major initial mechanism in a cascade of events finally leading to neurotoxicity and cell death in Alzheimer's disease.
Müller
W E
WE
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Eckert
G P
GP
Scheuer
K
K
Cairns
N J
NJ
Maras
A
A
Gattaz
W F
WF
D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D004161:Diphenylhexatriene / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; C098994:amyloid beta-protein (1-43); C074636:amyloid beta-protein (25-35); D004161:Diphenylhexatriene; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene