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

β-Amyloid protein (Aβ) 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 Aβ. Incubation of Aβ solutions at 37°C and pH 7.4 produces soluble oligomers in a concentration- dependent manner. Fresh Aβ42 solutions rapidly form soluble oligomers, whereas Aβ40 solutions require prolonged incubation to produce oligomers. Fresh Aβ42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Aβ40 solutions, possibly mediated by soluble oligomers. The differences between Aβ42 and Aβ40 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 Aβ peptides which gives high yield and purity of the initial crude preparation.