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

The central question related to beta-amyloidogenesis is how amyloid beta-protein (Abeta) 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 Abeta42(43), which is believed to be an initially deposited Abeta species, as a probe. In that study, we found that Abeta42 is bound to membranes in brains with abundant diffuse plaques, and that the bound lipid is likely GM1 ganglioside. To further characterize this novel Abeta species, we investigated its reactivity to cholera toxin, and performed immunoprecipitation experiments using several anti-Abeta monoclonal antibodies. The immunoprecipitates obtained with BAN052 (specific for the N-terminus of Abeta), but not BC05 and 4G8 (specific for Abeta17-24), showed significant Abeta immunoreactivity and cholera toxin reactivity. The present results strongly suggest that Abeta binds to a GM1 ganglioside in such a way that the bound Abeta is only recognized by BAN052, of the monoclonal antibodies used in this study.