SULFATED COMPOUNDS ATTENUATE BETA-AMYLOID TOXICITY BY INHIBITING ITS ASSOCIATION WITH CELLS

AGENTS that interfere with the toxic effects of beta-amyloid protein m ay be therapeutically useful against Alzheimer's disease. We reported recently that several sulphated glycosaminoglycans and sulphonated dye s attenuate the toxic effects of beta-amyloid fragments beta 25-35 and beta 1-40 in two clonal cell lines. We now demonstrate that this prot ective effect is due to interference with beta-amyloid cell associatio n rather than effects on beta-amyloid structure. Using an enzyme-linke d immunoabsorbance assay to detect cell-associated beta 1-40, we found in a range of compounds a strong correlation between inhibition of He La cell association of beta 1-40 and attenuation of cellular toxicity as measured by inhibition of [4,5-dimethylthiazol-2-yl]-2,5-diphenylte trazolium bromide (MTT) reduction. In contrast, effects on peptide str ucture, as measured by Congo red binding, were generally inconsistent with the attenuating effects of the compounds on cellular toxicity. Th ese results suggest that by binding beta-amyloid these agents prevent its interaction with cells.