Transthyretin (TTR) is a transport protein in plasma for thyroid hormone and forms a complex with retinol-binding protein. It has a potential to form amyloid fibrils and two major clinical forms are known: senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP). It has been shown that transthyretin (TTR) exists in different molecular variants. Besides point mutations associated with different diseases such as amyloidosis, other molecular variants occur that might be of scientific interest. The aim of our study was to investigate the role of TTR in human longevity in a sardinian elderly population. In this study we have considered 40 DNA and plasma samples taken from individuals who belong to different ages, (80-89years, 90-99years, 100-104years; 20-50years) and used genomic and proteomic approaches. The plasma proteins have been analyzed trough 2D-PAGE and mass spectrometry. The DNA sequencing was performed on the two exons (exons 2 and 3) of the transthyretin gene. The results of qualitative and quantitative analysis show some important variations in the expression of TTR in the groups of plasma samples studied. Particularly, we have observed a significative absence of one spot of TTR in about 60% of the groups 90-99y and 100-104y and a significative intensity decrease of the same spot only in the group 100-104years. The results of DNA sequencing show that some point mutation are more frequent in the group 90-99years than in the other groups studied.