Abstract

Cell culture systems for evaluating the biological effects of the β-amyloid protein are potentially important tools in the study of the pathogenesis of Alzheimer's disease. In this report, methodological considerations in the assessment of β-amyloid neurotoxicity are discussed. Chronic incubation of β01–40 in primary human cortical cultures results progressive neuronal degeneration. The neurodegenerative process occurs in association with localized deposition of β-amyloid on the neuronal soma ultimately resulting in the formation of compact β-amyloid deposits. A β1–40 preparation from another laboratory was tested that did not form neuronal β-amyloid deposits and was not neurotoxic. Thus, the conformational state of the β1–40 peptide leading to the formation of neuronal amyloid deposits is an important determinant of neurotoxicity. Variables in peptide preparation that influence this property may account for variation in neurotoxic potency.

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