BETA-AMYLOID PEPTIDE INVITRO TOXICITY - LOT-TO-LOT VARIABILITY

BetaA4 peptide (betaAP) accumulates in amyloid plaques of Alzheimer's disease and may contribute to neuronal degeneration. Conflicting observations have been reported regarding the direct in vitro and in vivo neurotoxicity of betaAP. We have assessed in vitro betaAP toxicity in high density primary rat hippocampal cultures and found marked lot-to-lot differences in the neurotoxic properties of betaAP. One lot of betaAP from a commercial supplier resulted in significant direct neurotoxicity at 10 muM, while 2 other lots from the same supplier were essentially nontoxic. Three additional lots of betaAP from unrelated sources were also nontoxic at 10 muM. Initial biochemical characterization has not yet revealed any marked differences among the various lots of betaAP. Low levels of endotoxin (ca., 1 EU/ml) were detected in several betaAP preparations but did not correlate with neurotoxicity. Our observation that lot-to-lot variability of betaAP occurred even under identical in vitro culture conditions may account for part of the present controversy in this area.