The toxic effects of beta -amyloid (A beta) (1-42), apolipoprotein E (apoE) isoforms, and apoE/A beta complexes were studied in human SH-SY5Y neuroblastoma cells and fibroblasts using MTT reduction. In SH-SY5Y cells, A beta (1-42) gave time-dependent toxicity over 2-48 h, which was reduced by co-incubation with rabbit beta -very low density lipoproteins (beta -VLDL). Human recombinant apoE3 and E4 isoforms were also toxic by themselves and also potentiated A beta effects when used alone, but not when associated with beta -VLDL. None of the treatments were toxic to human fibroblasts. These results suggest that beta -VLDL has a protective role on A beta -induced neurotoxicity and that the status of apoE or the conformation of lipoprotein containing apoE particles may be important for determining the contribution of apoE to neurodegeneration. NeuroReport 12:201-206 (C) 2001 Lippincott Williams & Wilkins.