Reference: FASEB J 1997; Vol. 11, A961.


N.V. Koudinova1,2, A.R. Koudinov1,2,  A. Kumar2 and T.T. Berezov1

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

2. Department of Pathology and Medicine, New York University Medical Center, 560 First Avenue, New York, NY 10016, USA

It is known that in normal human plasma and CSF the soluble form of Alzheimer's amyloid beta protein (sAb) is complexed to HDL and that Ab protein participates in lipid metabolism. Nevertheless, it is not known to which HDL structural constituent sAb is primarily bound. Herein we report further studies of Ab to HDL interaction in an in vitro system using biotinylated Ab1-40 as an sAb tracer and normal human plasma HDL. Purified HDLs were incubated with the peptide followed by the lipoprotein repurification by Size Exclusion (SE) HPLC. SDS/PAGE followed by Immunoblot and N-terminal sequence analysis of the corresponding protein bands revealed that Ab is bound to many apolipoproteins of the HDL, mainly apoA-I, apoA-II, apoE and apoJ. On the other hand, reconstituted protein free HDL also binds Ab peptide and inhibits its aggregation, as intact HDL does. This was assessed by SE-HPLC, SDS/PAGE, immunoblot analysis and ultrastructural electron microscopic studies, thioflavine T assay and Congo Red staining for b amyloid fibrils. Ab binding to both lipids and apolipoproteins may modulate the peptide to HDL association and be particularly relevant to Ab normal biology, physiology and the disease.

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