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.
El-Agnaf
O M
OM
Neurodegeneration Unit, Department of Surgery, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 0RE, United Kingdom. oelagna@sghms.ac.uk
Mahil
D S
DS
Patel
B P
BP
Austen
B M
BM
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D001704:Biopolymers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)