Reference: Neurosci Lett 1997; Vol. 48, S29.


A.R. Koudinov, N.V. Koudinova, G.Sh. Burbaeva, K. Kozirev, T.T. Berezov, V.Yu.Uvarov and Yu.D. Ivanov

Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation

Amyloid b (Ab) is a major constituent of amyloid deposits in brain tissue of Alzheimer's and Down's syndrome patients and is a normal soluble protein (sAb) in humans. We showed previously that sAb in both normal plasma and CSF is associated with high density lipoprotein (HDL) and that the peptide is involved in lipid metabolism. The aim of the present work was to elucidate whether lipid as an important HDL structural constituent contributes to sAb to HDL binding and solubility. To this end we studied the binding of Ab1-40 to protein free normal plasma HDL lipid particles by density ultracentrifugation, gel filtration, SDS/PAGE,  Immunoblot analysis, ultrastructural electron microscopy of Ab morphology and Congo Red staining and thioflavine T assay for b amyloid fibrils. The effect of HDL phospholipid on the Ab1-40 secondary structure was calculated from the Raman spectra of the peptide in the presence of dimiristoylphosphatidylcholine proteoliposomes, obtained in the amide-I band, and confirmed by the listed above methods. Conformation of the Ab, calculated for a-helix, b-strand, b-turn and coil was found to be 2:58:26:14 and 13:53:21:13 for lipid free and proteoliposome bound peptide, respectively. These data imply that HDL lipid, and in particular, phospholipid, binding to sAb contributes to the b-peptide  solubility in biological fluids and inhibits its fibrillogenic b-strand conformation. Change of this interaction in the disease may drive peptide's polymerization into the brain tissue amyloid fibrils.

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