Amyloid β-protein (Aβ) associated with lipid molecules: immunoreactivity distinct from that of soluble Aβ

AbstractWe previously identified a novel amyloid β-protein (Aβ), that binds to GM1 ganglioside, in brains exhibiting the early pathological changes of AD. In this study, we raised monoclonal antibodies, using membrane fractions containing abundant GM1 ganglioside-bound Aβ as antigens. Monoclonal antibody 4396, produced in this study, immunoprecipitates Aβ42 in the membrane fractions of brains with diffuse plaques, but does not react with soluble Aβ42 or GM1 ganglioside. Furthermore, this antibody recognizes the Aβ bound to lipid vesicles containing GM1 ganglioside, and unexpectedly, phosphatidylinositol. In contrast, a control anti-Aβ monoclonal antibody does not recognize the Aβ bound to these lipid vesicles. These results indicate that Aβ associated with lipids has an immunoreactivity distinct from that of soluble A