Aggregation of Secreted Amyloid -Protein into Sodium Dodecyl Sulfate-stable Oligomers in Cell Culture

Filamentous aggregates of the 40-42-residue amyloid β-protein (Aβ) accumulate progressively in the limbic and cerebral cortex in Alzheimer's disease, where they are intimately associated with neuronal and glial cytopathology. Attempts to model this cytotoxicity in vitro using synthetic peptides have shown that monomeric Aβ is relatively inert, whereas aggregated Aβ reproducibly exerts a variety of neurotoxic effects. The processes that mediate the conversion of monomeric Aβ into a toxic aggregated state are thus of great interest. Previous studies of this conversion have employed high concentrations (10 -10 M ) of synthetic Aβ peptides under nonbiological conditions. We report here the detection of small amounts (