Amplification techniques and diagnosis of prion diseases

• Published in: Revue neurologique Vol. 175; no. 7-8; pp. 458 - 463
• Main Authors: Brandel, J.-P., Culeux, A., Grznarova, K., Levavasseur, E., Lamy, P., Privat, N., Welaratne, A., Denouel, A., Laplanche, J.-L., Haik, S.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-09-2019; Elsevier Masson
• Subjects: Amplification techniques; Creutzfeldt-Jakob Syndrome - diagnosis; Creutzfeldt-Jakob Syndrome - microbiology; Humans; Life Sciences; Molecular Diagnostic Techniques - methods; PMCA; Prion; Prion Diseases - diagnosis; Prion Diseases - microbiology; RT-QuIC; Prion; Amplification techniques; PMCA; RT-QuIC
• ISSN: 0035-3787
• DOI: 10.1016/j.neurol.2019.06.002

Protein misfolding cyclic amplification assay (PMCA) and real-time quaking-induced conversion (RT-QuIC) are two amplification techniques based on the ability of PrPsc to induce a conformational change in PrP allowing the detection of minute amounts of PrPsc in body fluids or tissues. PMCA and RT-QuIC have different ability to amplify PrPsc from sporadic, variant and genetic forms of Creutzfeldt-Jakob disease (CJD). PMCA readily amplifies PrPsc from variant CJD (vCJD) tissue while RT-QuIC easily amplifies PrPsc from sporadic CJD (sCJD) patient tissues. In terms of diagnosis, this implies the possibility of distinguishing vCJD from sCJD and explains the wider use of RT-QuIC given the respective frequencies of vCJD and sCJD. The sensitivity values of RT-QuIC for the diagnosis of sCJD are comparable or higher than those of the other tests (EEG, MRI, detection of 14-3-3 or tau proteins in cerebrospinal fluid) but with a specificity close to 100%. These new diagnostic methods could also be useful for the diagnosis of other neurodegenerative diseases.