Amyloid-β is an antioxidant for lipoproteins in cerebrospinal fluid and plasma

Amyloid-beta (A beta) 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 A beta secretion remains unknown. Here we show that at the concentrations measured in biological fluids (0.1-1.0 nM), A beta (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. A beta (1-40) also inhibited copper-catalyzed LDL oxidation when added in molar excess of copper, but did not influence oxidation induced by an ate-initiator. Other A beta peptides also possessed antioxidant activity in the order A beta (1-40) > A beta (1-42) > A beta (25-35), whereas A beta (35-25), was inactive. These data suggest that A beta (1-40), may act as a physiological antioxidant in CSF and plasma lipoproteins, functioning by chelating transition metal ions. (C) 2000 Elsevier Science Inc.