Oligomerization and toxicity of beta-amyloid-42 implicated in Alzheimer's disease

beta-Amyloid protein (Abeta) is the major component of senile plaques found in the brains of Alzheimer's patients. A novel ELISA has been developed which probes the early stages of oligomerization of Abeta. Incubation of Abeta solutions at 37 degrees C and pH 7.4 produces soluble oligomers in a concentration-dependent manner. Fresh Abeta42 solutions rapidly form soluble oligomers, whereas Abeta40 solutions require prolonged incubation to produce oligomers. Fresh Abeta42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Abeta40 solutions, possibly mediated by soluble oligomers. The differences between Abeta42 and Abeta40 could explain the association of the longer form with familial early-onset Alzheimer's disease. We also report a new strategy for solid-phase synthesis of Abeta peptides which gives high yield and purity of the initial crude preparation.