Predicting the in vitro toxicity of synthetic beta-amyloid (1-40).

The in vitro toxicity of synthetic beta-amyloid (betaA4) is variable and unpredictable, limiting its use as a research tool. This study describes a method using Congo red (CR) to predict the in vitro toxicity of betaA4 solutions. Histopathologically, CR is used to stain the neuritic, betaA4-containing plaques, one of the hallmarks of Alzheimer's disease. In this study, synthetic betaA4 solutions were incubated with CR at a molar ratio of 1.0:2.5. The solutions were centrifuged and the absorbance of the supernatants were measured. Predictions of nontoxicity correlated with absorbance readings near zero. Toxicity was evaluated relative to control cells (vehicle only), using a hemocytometer to count PC-12 cells that excluded trypan blue. The positive predictive value of the test was 78% and the negative predictive value was 100%. To use this test, the toxic concentration(s) of betaA4 must first be established empirically. Then, the CR test can be used to evaluate the potential toxicity of betaA4 solutions at similar concentrations. Thus, this test can be used under a variety of laboratory circumstances.