ALZHEIMER'S AMYLOID b AND LIPID METABOLISM
A.R. Koudinov, N.V. Koudinova and T.T. Berezov
Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation
Although amyloid b (Ab) is a major constituent of Alzheimer's brain amyloid, it is a normal soluble protein (sAb) of plasma and cerebrospinal fluid (CSF). We showed recently that sAb in both plasma and CSF is associated with high density lipoproteins. This imply that sAb is involved in lipid metabolism, as many other protein constituents of lipoproteins do. To test this possibility we first evaluated the effect of synthetic Ab1-40 and Ab1-28 on plasma cholesterol esterification by colorimetric measuring of the decrease in the mass of endogenous unesterified cholesterol in the incubated plasma samples. Both peptides at a concentration of 1 ng/ml inhibited plasma cholesterol esterification rate to 40-50% of control value. We also tested the effect of Ab on lipid biosynthesis in HepG2 cells. Treatment of cells with different concentrations of Ab1-40 decreased the syntheses of various [14C]-acetate radiolabeled lipid species. The lipids whose synthesis was decreased most were free and esterified cholesterol and phospholipids. Synthesis of triacylglycerols was also reduced but to a lower extent. Our data suggest that Ab has extended functions in lipid metabolism. The observed effect may be of special importance in pathological condition, and contribute to the neurodegeneration, in Alzheimer's disease and related disorders.
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