Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid andplasma

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 c an be found in low concentrations in cerebrospinal fluid (CSF) and plasma, where it is associated with lipoproteins. However, the physiological role o f 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 inhibit s autooxidation of CSF lipoproteins and plasma low density lipoprotein (LDL ). At higher concentrations of the peptide its antioxidant action was aboli shed. A beta (1-40) also inhibited copper-catalyzed LDL oxidation when adde d 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 p hysiological antioxidant in CSF and plasma lipoproteins, functioning by che lating transition metal ions. (C) 2000 Elsevier Science Inc.