Oligomerization and Toxicity of β-Amyloid-42 Implicated in Alzheimer's Disease☆

b-Amyloid protein (Ab) 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 Ab. Incubation of Ab solutions at 37°C and pH 7.4 produces soluble oligomers in a concentration-dependent manner. Fresh Ab42 solutions rapidly form soluble oligomers, whereas Ab40 solutions require prolonged incubation to produce oligomers. Fresh Ab42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Ab40 solutions, possibly mediated by soluble oligomers. The differences between Ab42 and Ab40 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 Ab peptides which gives high yield and purity of the initial crude preparation. © 2000 Academic Press