Transthyretin inhibition of amyloid beta aggregation and toxicity

Objectives: The aim of this study was to investigate transthyretin (prealbumin) effects on Aβ25–35-induced cytotoxicity. Design and methods: In view of the well-recognized literature data demonstrating that Aβ25–35 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. Results: Incubation of Aβ25–35 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 Aβ25–35. Conclusions: 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.