The article investigates the structure and biological activity of protofibrils, intermediate stages in the fibrillogenesis of amyloid β-protein (Aβ), a key component of Alzheimer's disease (AD) amyloid deposits. The authors used size exclusion chromatography to isolate low molecular weight Aβ (LMW Aβ) and protofibrils, and characterized their properties. They found that protofibrils are in equilibrium with LMW Aβ, can form fibrils, and exhibit characteristics similar to mature fibrils, such as binding to Congo red and thioflavin T dyes. Protofibrils also showed significant β-sheet content and biological activity, altering the metabolism of cultured neurons. These findings suggest that protofibrils are important intermediates in the fibrillogenesis process and may play a role in the neurotoxicity associated with AD. The study provides insights into the mechanisms of fibril formation and potential therapeutic targets for AD.The article investigates the structure and biological activity of protofibrils, intermediate stages in the fibrillogenesis of amyloid β-protein (Aβ), a key component of Alzheimer's disease (AD) amyloid deposits. The authors used size exclusion chromatography to isolate low molecular weight Aβ (LMW Aβ) and protofibrils, and characterized their properties. They found that protofibrils are in equilibrium with LMW Aβ, can form fibrils, and exhibit characteristics similar to mature fibrils, such as binding to Congo red and thioflavin T dyes. Protofibrils also showed significant β-sheet content and biological activity, altering the metabolism of cultured neurons. These findings suggest that protofibrils are important intermediates in the fibrillogenesis process and may play a role in the neurotoxicity associated with AD. The study provides insights into the mechanisms of fibril formation and potential therapeutic targets for AD.