A NOVEL SERUM MICRORNA SIGNATURE TO SCREEN TRANSTHYRETIN-RELATED FAMILIAL AMYLOID POLYNEUROPATHY

Familial amyloid polyneuropathy (FAP), associated with mutations in the transthyretin (TTR) gene, is the most common form of genetic amyloidosis. It is a progressive devastating disease presenting with a heterogeneous spectrum of manifestations, thus diagnosis is often overlooked. Given that TTR amyloidosis is now susceptible of treatment and early diagnosis provides for better prognosis, potential biomarkers are needed. In peripheral nerves, suggested pathogenic mechanisms include endoneurial oedema, nerve ischemia, oxidative stress, inflammation, and apoptosis. Recently, circulating microRNAs (miRNAs) have been described as promising diagnostic biomarkers in many chronic and degenerative neurological disorders. Our aim was to perform serum miRNA profiling in patients carrying a TTR mutation, using quantitative reverse transcription polymerase chain reaction (qRT-PCR) of an array panel containing approximately 836 human miRNAs. Preliminary results showed in TTR-FAP patients vs normal controls an overexpression of 28 miRNAs whereas 16 miRNAs were down-regulated. Moreover, target scan tools showed that the miRNAs overexpressed in FAP patients are involved in autophagy and apoptosis processes. Although our results need further confirmation, the findings suggest miRNAs as potential biomarkers to better understand the pathogenic mechanisms and to monitor the disease course.