Methodological variables in the assessment of beta amyloid neurotoxicity

Cell culture systems for evaluating the biological effects of the beta-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 beta-amyloid neurotoxicity are discussed. Chronic incubation of beta 1-40 in primary human cortical cultures results in progressive neuronal degeneration. The neurodegenerative process occurs in association with localized deposition of beta-amyloid on the neuronal soma ultimately resulting in the formation of compact beta-amyloid deposits. A beta 1-40 preparation from another laboratory was tested that did not form neuronal beta-amyloid deposits and was not neurotoxic. Thus, the conformational state of the beta 1-40 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.