Alzheimer's Soluble Amyloid Beta Protein Is Secreted by Hepg2 Cells as an Apolipoprotein

Abstract

Recently we reported that the soluble form of amyloid beta protein (sA beta) in normal human plasma and cerebrospinal fluid is associated with lipoprotein (LP) particles. In this paper we tested the sA beta secretion by cells in association with LP in the model of the human hepatoma HepG2 cell line. These cells secreted sA beta to the culture media and expressed intracellular sA beta immunoreactivity. Soluble A beta in the cell supernatant was detected in 200-300 kDa LP complexes in association with apoA-I, apoJ, transthyrethin and phospholipids, triglycerides and free and esterified cholesterol. This was assessed by size exclusion HPLC, immunoprecipitation with corresponding antibodies and by analysis of sA beta associated metabolically-labeled lipids, respectively. Our results suggest that sA beta to LP association represents a unique mechanism, governing the normal biology of sA beta.

Three-dimensional colocalization analysis of plasma-derived apolipoprotein B with amyloid plaques in APP/PS1 transgenic mice

“…In blood, signiWcant A is associated the triglyceriderich lipoproteins (TRLs) (Mamo et al 2008) consistent with the Wndings by Koudinov and Koudinova (1997), who found that hepatocytes secrete A exclusively as a lipoprotein complex. In recent studies, we reported that the absorptive epithelial cells of the small intestine (enterocytes) have substantial abundance of A , secreted into blood associated with dietary induced lipoproteins (chylomicrons) (Galloway et al 2007).…”

Lipid peroxidation and Alzheimer’s disease: Key role of Amyloid-β

“…It remains indeterminate whether Ab is present in biological fluids as a part of a lipoprotein complex under stress conditions. Existence of such acute-phase Ab-lipoprotein complexes can be postulated taking into account consistent data on the association between Ab and HDL-like lipoproteins under normal conditions [11][12][13][14]. As described above, secreted Ab might be associated with a subset of small, dense, HDL-like lipoproteins.…”

“…Similarly, monomeric Ab co-isolates with lipoprotein particles from human plasma, in particular with the HDL and very high density lipoprotein (VHDL) fractions [12], and from AD brains [13]. Finally, human hepatoma HepG2 cells secrete Ab in the culture medium as a part of 200-300 kDa lipoprotein complexes in association with apolipoprotein (apo) A-I, apoJ, phospholipids, triglycerides and free and esterified cholesterol [14].…”

“…Ab appears to be tightly bound to lipoproteins in biological fluids, since no Ab reactivity is detected in lipoprotein-free fractions upon ultracentrifugation of CSF or plasma obtained from control subjects [11,12,14], which is well-known to cause a dissociation of weakly bound apolipoproteins from the lipoprotein surface [27]. Such tight association of Ab with lipoproteins is stronger than can be expected for purely hydrophobic interactions with lipids, suggesting that the peptide may equally bind to apolipoproteins (e.g., to apoE [28,29] and/or apoJ [26,30]), strengthening the association with lipoprotein particles.…”

High-Fat and Cholesterol Intake Affects Brain Homeostasis and Could Accelerate the Development of Dementia: A Systemic View

“…Koudinov et al [11] reported that hepatocytes secrete amyloid-β as a lipoprotein complex. Another organ where it has been documented that Aβ is produced is the small intestine.…”