The aim of this study was to investigate transthyretin (prealbumin) effects on Aβ 25–35 -induced cytotoxicity.In view of the well-recognized literature data demonstrating that Aβ 25–35 fibrillar aggregates cause in vitro cytotoxicity to human red blood cells and apoptotic changes to SK-N-BE neuroblastoma cells in cultures (ultrastructural evidence), we tested transthyretin effects on these two experimental models.Incubation of Aβ 25–35 with transthyretin (at transthyretin concentrations equal to CSF physiological levels) demonstrated both inhibition of red blood cells lysis and neutralization of SK-N-BE neuroblastoma cells ultrastructural apoptotic changes. Moreover, transthyretin was shown to be able to inhibit the formation of fibrillar macroaggregates of Aβ 25–35 .The findings imply that experimental systems investigating Aβ-induced cytotoxicity consider the protective interaction of transthyretin with Aβ; an interaction to be considered also in vivo in view of the fact that transthyretin immunoreactivity has been previously demonstrated in amyloid plaques of brains from Alzheimer’s disease patients.