ALZHEIMER'S SOLUBLE AMYLOID BETA PROTEIN IS ASSOCIATED WITH HIGH DENSITY LIPOPROTEINS IN NORMAL HUMAN CEREBROSPINAL FLUID AND IS SECRETED BY HEPG2 CELLS AS A PART OF LIPOPROTEIN COMPLEXES
A.R. Koudinov1,2*, N.V. Koudinova1,2, A. Kumar1, R.C. Beavis1 and J. Ghiso1
1. Department of Pathology and Pharmacology, New York University Medical Center, 560 First Avenue, New York, NY 10016, USA
2. Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation
The soluble form of amyloid b protein (sAb) is associated with high density lipoprotein (HDL) in normal human plasma (Biochem Biophys Res Commun (1994) 205, 1164-71). This suggests that sAb to HDL association is rather a more general phenomenon taking place in other biological fluids and tissues. To ascertain this hypothesis the colocalization of sAb with lipoproteins (LP) was investigated in cerebrospinal fluid (CSF) and in cell culture supernatant. Normal human CSF LPs were obtained by sequential flotation ultracentrifugation and analyzed for the presence of sAb via immunoblot, size-exclusion HPLC, immunoelectron microscopy, N-terminal sequence and mass-spectrometry analyses. Soluble Ab was associated with ~200 kDa CSF-HDL particles of 16.8 ± 3.2 nm in diameter. A ~4.3 kDa component purified by reverse phase HPLC was immunoreactive with anti-Ab antibodies, exhibited an N-terminal sequence identical to the Ab peptide and a mass of 4325.1 Da, and therefore indicates that the main sAb specie associated with CSF-HDL is sAb1-40. The sAb secretion by cells in association with LPs was tested in human hepatoma HepG2 cell line. Soluble Ab in the cell culture supernatant was detected in ~200 kDa molecular mass LP complexes in association with apoJ, apoA-I, phospholipids, triglycerides and free and esterified cholesterol. Our results suggest that the association of sAb with LP represents a common mechanism for the peptide transport in biological fluids.
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