GM1 ganglioside-bound amyloid β-protein in Alzheimer's disease brain

The central question related to beta-amyloidogenesis is how amyloid beta-protein (A beta) is generated and deposited. To address this issue, we investigated the early stage of beta-amyloidogenesis using cerebral cortices from Alzheimer's disease and Down's syndrome patients and normal aged individuals with BC05, a specific monoclonal antibody for A beta 42(43), which is believed to be an initially deposited A beta species, as a probe. In that study, we found that A beta 42 is bound to membranes in brains with abundant diffuse plaques, and that the bound lipid is likely GM1 ganglioside. To further characterize this novel A beta species, we investigated its reactivity to chorela toxin, and performed immunoprecipitation experiments using several anti-A beta monoclonal antibodies. The immunoprecipitates obtained with BAN052 (specific for the N-terminus of A beta), but not BC05 and 4G8 (specific for A beta 17-24), showed significant A beta immunoreactivity and cholera toxin reactivity. The present results strongly suggest that A beta binds to a GM1 ganglioside in such a way that the bound A beta is only recognized by BAN052, of the monoclonal antibodies used in this study. (C) 1998 Elsevier Science Inc.