Amplification techniques and diagnosis of prion diseases

J-P Brandel; A Culeux; K Grznarova; E Levavasseur; P Lamy; N Privat; A Welaratne; A Denouel; J-L Laplanche; S Haik

doi:10.1016/j.neurol.2019.06.002

Amplification techniques and diagnosis of prion diseases

Rev Neurol (Paris). 2019 Sep-Oct;175(7-8):458-463. doi: 10.1016/j.neurol.2019.06.002. Epub 2019 Jul 8.

Authors

J-P Brandel¹, A Culeux², K Grznarova², E Levavasseur², P Lamy², N Privat², A Welaratne³, A Denouel², J-L Laplanche⁴, S Haik⁵

Affiliations

¹ Sorbonne Université, Inserm, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; AP-HP, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, 47, boulevard de l'Hôpital, 75013 Paris, France. Electronic address: jean-philippe.brandel@aphp.fr.
² Sorbonne Université, Inserm, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France.
³ AP-HP, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, 47, boulevard de l'Hôpital, 75013 Paris, France.
⁴ AP-HP, Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, Université Paris Descartes, 2, rue Ambroise-Paré 75010 Paris, France.
⁵ Sorbonne Université, Inserm, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; AP-HP, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, 47, boulevard de l'Hôpital, 75013 Paris, France.

PMID: 31296398
DOI: 10.1016/j.neurol.2019.06.002

Abstract

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.

Keywords: Amplification techniques; PMCA; Prion; RT-QuIC.

Publication types

Review

MeSH terms

Creutzfeldt-Jakob Syndrome / diagnosis*
Creutzfeldt-Jakob Syndrome / microbiology*
Humans
Molecular Diagnostic Techniques / methods
Prion Diseases / diagnosis*
Prion Diseases / microbiology*