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Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion

by Yamaguchi, Naohiro , Nakagaki, Takehiro , Yamada, Masahito , Matsubara, Takehiro , Sano, Kazunori , Satoh, Katsuya , Fuse, Takayuki , Yamanaka, Hitoki , Mizusawa, Hidehiro , Nishida, Noriyuki , Ishibashi, Daisuke , Collins, Steven J , Atarashi, Ryuichiro , Shirabe, Susumu , Kitamoto, Tetsuyuki , Klug, Genevieve , McGlade, Amelia

in 631/1647 / 631/45/460 / 692/699/375/1937 / 692/700/139 / Bioassays / Biomarkers - cerebrospinal fluid / Biomedical and Life Sciences / Biomedical research / Biomedicine / Body fluids / Brain - metabolism / brief-communication / Cancer Research / Cerebrospinal fluid / Creutzfeldt-Jakob disease / Creutzfeldt-Jakob Syndrome - cerebrospinal fluid / Creutzfeldt-Jakob Syndrome - diagnosis / Diagnosis / Fluorescent Dyes / Humans / Infectious Diseases / Metabolic Diseases / Molecular Medicine / Motion / Neurosciences / Physiological aspects / Prions / Prions - cerebrospinal fluid / PrPSc Proteins - cerebrospinal fluid / Sensitivity and Specificity / Spinal cord / Thiazoles

2011

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Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion

2011

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Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion

2011

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Journal Article

Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion

Yamaguchi, Naohiro,

Nakagaki, Takehiro,

Yamada, Masahito,

Matsubara, Takehiro,

Sano, Kazunori,

Satoh, Katsuya,

Fuse, Takayuki,

Yamanaka, Hitoki,

Mizusawa, Hidehiro,

Nishida, Noriyuki,

Ishibashi, Daisuke,

Collins, Steven J,

Atarashi, Ryuichiro,

Shirabe, Susumu,

Kitamoto, Tetsuyuki,

Klug, Genevieve,

McGlade, Amelia

2011

Overview

Definitive diagnosis of prion disease currently requires postmortem brain tissue. Now, Ryuichiro Atarashi and colleagues have discovered an assay that can identify prions in human cerebrospinal fluid. This assay could allow for diagnosis of disease in living humans. The development of technologies for the in vitro amplification of abnormal conformations of prion protein (PrP Sc ) has generated the potential for sensitive detection of prions. Here we developed a new PrP Sc amplification assay, called real-time quaking-induced conversion (RT-QUIC), which allows the detection of ≥1 fg of PrP Sc in diluted Creutzfeldt-Jakob disease (CJD) brain homogenate. Moreover, we assessed the technique first in a series of Japanese subjects and then in a blind study of 30 cerebrospinal fluid specimens from Australia, which achieved greater than 80% sensitivity and 100% specificity. These findings indicate the promising enhanced diagnostic capacity of RT-QUIC in the antemortem evaluation of suspected CJD.

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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

/ Biomarkers - cerebrospinal fluid

/ Biomedical and Life Sciences