Effect of amyloid peptides on serum withdrawal-induced cell differentiation and cell viability.

Abnormal deposition of amyloid-beta(A beta) peptides and formation of neuritic plaques are recognized as pathological processes in Alzheimer's disease (AD) brain. By using amyloid precursor protein (APP) transfected cells, this study aims to investigate the effect of overproduction of A beta on cell differentiation and cell viability. It was shown that after serum withdrawal, untransfected cell (N2a/Wt) and vector transfected cells (N2a/vector) extended long and branched cell processes, whereas no neurites was induced in wild type APP (N2a/APP695) and Swedish mutant APP (N2a/APPswe) transfected N2a cells. After differentiation by serum withdrawal, the localization of APP/A beta and neurofilament was extended to neurites, whereas those of APP-transfected cells were still restricted within the cell body. Levels of both APP and A beta were significantly higher in N2a/APP695 and N2a/APPswe than in N2a/Wt, as determined by Western blot and Sandwich ELISA, respectively. To further investigate the effect of A beta on the inhibition of cell differentiation, we added exogenously the similar level or about 10-times of the A beta level produced by N2a/APP695 and N2a/APPswe to the culture medium and co-cultured with N2a/Wt for 12 h, and we found that the inhibition of serum withdrawal-induced differentiation observed in N2a/APP695 and N2a/APPswe could not be reproduced by exogenous administration of A beta into N2a/Wt. We also observed that neither endogenous production nor exogenous addition of A beta 1-40 or A beta 1- 42, even to hundreds fold of the physiological concentration, affected obviously the cell viability. These results suggest that the overproduction of A beta could not arrest cell differentiation induced by serum deprivation and that, at least to a certain degree and in a limited time period, is not toxic to cell viability.