Abstract : Prion diseases are characterised by the accumulation of an abnormal isoform of the prion protein (PrPsc) in different tissues. Biological diagnosis is based on the determination of the protein 14.3.3 in cerebro-spinal fluid (CSF). On the same samples, adding the determination of neopterin increases the specificity of the protein 14.3.3. Nevertheless, analytical characteristics of the protein 14.3.3 determination are not sufficient to ascertain the diagnosis during life-time. We then proposed to assess the presence of the direct marker, the PrPsc resistant to proteinase K (PrPres), in peroneal nerves. The weak sensitivity of the technique developed (1 positive sample about 3) encouraged us to use and validate an external ligand, streptomycin, in order to concentrate the PrPsc. We demonstrated the ability of the streptomycin to act as a precipitating agent for PrPsc on brain and tonsil samples. The analytical sensitivity was comparable to this obtain after phosphotungstic acid precipitation with small quantity of initial tissue (5 mg). Moreover, using a significant number of brain samples, patients with TSE were accurately classified from those without TSE with sensitivity and specificity to 100 %. We then propose to test this protocol on nerves samples biopsies.