Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid and plasma.
Amyloid-beta (Abeta) peptide, a major constituent of senile plaques and a hallmark of Alzheimer's disease (AD), is normally secreted by neurons and can be found in low concentrations in cerebrospinal fluid (CSF) and plasma, where it is associated with lipoproteins. However, the physiological role of Abeta secretion remains unknown. Here we show that at the concentrations measured in biological fluids (0.1-1.0 nM), Abeta(1-40) strongly inhibits autooxidation of CSF lipoproteins and plasma low density lipoprotein (LDL). At higher concentrations of the peptide its antioxidant action was abolished. Abeta(1-40) also inhibited copper-catalyzed LDL oxidation when added in molar excess of copper, but did not influence oxidation induced by an azo-initiator. Other Abeta peptides also possessed antioxidant activity in the order Abeta(1-40) > Abeta(1-42) > Abeta(25-35), whereas Abeta(35-25) was inactive. These data suggest that Abeta(1-40) may act as a physiological antioxidant in CSF and plasma lipoproteins, functioning by chelating transition metal ions.
Kontush
A
A
Medical Clinic, University Hospital Eppendorf, Hamburg, Germany. kontush@uke.uni-hamburg.de
Berndt
C
C
Weber
W
W
Akopyan
V
V
Arlt
S
S
Schippling
S
S
Beisiegel
U
U
D000328:Adult; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D019787:Linoleic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood* / Q000134:cerebrospinal fluid*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; C099252:oxidized low density lipoprotein; D003300:Copper; D002784:Cholesterol; D019787:Linoleic Acid; D006861:Hydrogen Peroxide