GM1 Ganglioside-Bound Amyloid β-Protein in Alzheimer’s Disease Brain

The central question related to β-amyloidogenesis is how amyloid β-protein (Aβ) is generated and deposited. To address this issue, we investigated the early stage of β-amyloidogenesis using cerebral cortices from Alzheimer’s disease and Down’s syndrome patients and normal aged individuals with BC05, a specific monoclonal antibody for Aβ42(43), which is believed to be an initially deposited Aβ species, as a probe. In that study, we found that Aβ42 is bound to membranes in brains with abundant diffuse plaques, and that the bound lipid is likely GM1 ganglioside. To further characterize this novel Aβ species, we investigated its reactivity to chorela toxin, and performed immunoprecipitation experiments using several anti-Aβ monoclonal antibodies. The immunoprecipitates obtained with BAN052 (specific for the N-terminus of Aβ), but not BC05 and 4G8 (specific for Aβ17–24), showed significant Aβ immunoreactivity and cholera toxin reactivity. The present results strongly suggest that Aβ binds to a GM1 ganglioside in such a way that the bound Aβ is only recognized by BAN052, of the monoclonal antibodies used in this study.