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.
Busciglio
J
J
Department of Neurology, Harvard Medical School, Boston, MA 02115.
Lorenzo
A
A
Yankner
B A
BA
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D009420:Nervous System / Q000187:drug effects / Q000473:pathology*
D016229:Amyloid beta-Peptides