ALZHEIMER'S SOLUBLE AMYLOID BETA PROTEIN IS NOT SECRETED BY INTESTINAL CACO-2 CELLS

A.R. Koudinov^1,2; T.T. Berezov¹; N.V. Koudinova^1,2

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

2. Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel

Amyloid b (Ab) is an important constituent of Alzheimer's and Down's syndrome brain amyloid and is a normal soluble human protein (sAb). Recently we reported that sAb in plasma and CSF is associated with high density lipoprotein (LP) and that sAb is secreted by hepatic cells complexed to the LP (FASEB J (1998) 12, 1097-99). However, the major sources of the LP in humans are hepatic and intestinal cells, but whether the latter cells are secreting sAb and if so whether sAb is apolipoprotein (apo) and/or lipid associated upon secretion or not was not known. We chose and tested intestinal Caco-2 cell line, widely used for different metabolic and LP syntheses studies. The results have shown, that although Caco-2 cells secreted into the media a significant amount of LP-lipid and apo A-I, A-II, A-IV, E, J and SAA (assessed by size exclusion HPLC, immunoblot analysis, immunoprecipitation with corresponding antibodies and by analysis of [14C]-acetate metabolically labeled lipids), they did not produce and secrete sAb. Taken together with our report on sAb secretion by hepatic cells current study suggests that hepatic (and not intestinal) cells may be an important source of the LP-associated systemic Ab.

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