AMYLOID BETA-PROTEIN (A-BETA) ASSOCIATED WITH LIPID MOLECULES - IMMUNOREACTIVITY DISTINCT FROM THAT OF SOLUBLE A-BETA

We previously identified a novel amyloid P-protein (A beta), that bind s to GM1 ganglioside, in brains exhibiting the early pathological chan ges of AD, In this study, we raised monoclonal antibodies, using membr ane fractions containing abundant GM1 ganglioside-bound A beta as anti gens, Monoclonal antibody 4396, produced in this study, immunoprecipit ates A beta 42 in the membrane fractions of brains with diffuse plaque s, but does not react with soluble A beta 42 or GM1 ganglioside, Furth ermore, this antibody recognizes the AP bound to lipid vesicles contai ning GM1 ganglioside, and unexpectedly, phosphatidylinositol. In contr ast, a control anti-A beta monoclonal antibody does not recognize the A beta bound to these lipid vesicles, These results indicate that A be ta associated with lipids has an immunoreactivity distinct from that o f soluble A. (C) 1997 Federation of European Biochemical Societies.