Changes in tissue proteome associated with ATTR amyloidosis: insights into pathogenesis.

In Transthyretin amyloidosis (ATTR), tissue deposition of transthyretin fibrils translates into a significant subversion of the tissues proteome. We used multidimensional protein identification technology for profiling the proteome of subcutaneous adipose tissue in patients with ATTR, in comparison with controls and patients with other types of amyloidoses, to identify the global proteomic changes related specifically with this disease. The adipose tissue proteome of five ATTR patients and 11 non-affected controls was analyzed. Samples from patients with Light Chain (AL) or reactive (AA) amyloidosis were studied alongside. In all ATTR samples, mass spectrometry data showed that transthyretin was specifically up-represented, being a marker of the nature of the deposits. Tissue resident proteins, involved in key biological processes, were also found to be differently represented compared to controls. The high-throughput analysis of the proteome of amyloid affected fat, combined with bioinformatic data interpretation, is a powerful tool for identification of perturbed protein expression in ATTR amyloidosis.